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  • 1. Beggs, J
    et al.
    Jordan, S
    Ericson, Ann-Charlott
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Craig, AD
    Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque2003In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 459, no 4, p. 334-354Article in journal (Refereed)
    Abstract [en]

    We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 ╡m, mean width = 1.29 ╡m) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 ╡m). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.

  • 2.
    Berg, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Ericson, Ann-Charlott
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Sjöstrand, Sven-Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Unique localization of eNOS-IR in human gastric mucosa.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. 5095-Conference paper (Other academic)
  • 3.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans2001In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 36, no 10, p. 1016-1021Article in journal (Refereed)
    Abstract [en]

    Background: Functional studies have shown that nitric oxide (NO) inhibits gastric acid secretion in a variety of species, including man. We have performed a morphological study with the intention of localizing the endothelial NO synthase (eNOS) in the human gastric mucosa.

    Methods: Fifteen healthy subjects voluntarily participated in the study, and mucosal biopsies were obtained from the cardia, corpus and antrum. The presence and localization of eNOS were studied using immunohistochemical techniques.

    Results: eNOS-immunoreactivity (eNOS-IR) is found in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close contact with parietal cells.

    Conclusions: eNOS-IR cells in close apposition to parietal cells provide morphological support for paracrine inhibition of gastric acid secretion by NO.

  • 4.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands2004In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 4, no 16Article in journal (Refereed)
    Abstract [en]

    Background

    Endothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.

    Methods

    Oxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [14C]aminopyrine.

    Results

    The histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA) enhanced the secretory response.

    Conclusion

    Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.

  • 5.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Grenegård, Magnus
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands2005In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 289, no 6, p. G1061-G1066Article in journal (Refereed)
    Abstract [en]

    We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

  • 6.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands2007In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 52, no 1, p. 126-136Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that nitric oxide (NO) inhibits histamine-induced gastric acid secretion in isolated human gastric glands. NO synthase has been found to be present in the human oxyntic mucosa and has been suggested to serve as a paracrine regulator of gastric acid secretion. Histamine stimulation of parietal cells induces cytoskeletal rearrangements, recruitment of H +/K +-ATPase-rich tubulovesicles to the apical membrane and expansion of intracellular canaliculi. The aim of the present study was thus to investigate (i) the effect of an NO donor on histamine-induced cytological transformations and (ii) the influence of increased [Ca 2+] i on NO-induced morphological changes in human parietal cells. Human gastric glands were isolated and subjected to the NO donor SNAP prior to histamine administration. [Ca 2+] i was increased by photolysis of the caged Ca 2+ compound NP-EGTA. The distribution of F-actin, ezrin, and H +/K +-ATPase was assessed by confocal microscopy. Ultrastructural analysis was performed using transmission electron microscopy. SNAP did not influence the histamine-induced translocation of F-actin, ezrin, and H +/K +-ATPase but prevented an increase in the canalicular size. Elevation of [Ca 2+] i in resting cells was found to mimic histamine-induced intraparietal cell transformations; however, NO-induced parietal cell morphology was unaffected by a rise in [Ca 2+] i. These results indicate that NO inhibits secretion of fluid into the canalicular lumen without affecting membrane recruitment and that this effect is Ca 2+-insensitive. © 2006 Springer Science+Business Media, Inc.

  • 7.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Synaptic organization of nociceptive relay nuclei in the cat and primate thalamus1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The fine structure of two thalamic nociceptive relay nuclei, the nucleus submedius (Sm) in the cat, and the posterior region in the owl monkey, was investigated using anatomical tract tracing techniques, immunohistochemical staining for neuroactive substances, and threedimensional reconstructions of synaptic circuitry.

    Ascending lamina I axons, labeled by anterograde transport of Phaseolus vulgaris leucoagglutinin, gave rise to two different types of termination in Sm: large, compact clusters of numerous boutons were predominant in the dense focus of the terminal field after a tracer injection at the site of nociceptive-specific neurons in lamina I, and boutons-of-passage type terminations were conspicuous in the periphery of a lamina I terminal field in Sm and predominant following a tracer injection at the site of thermoreceptive-specific neurons in lamina I. Three-dimensional reconstructions of a sample of these terminations, generated from series of ultrathin sections by using special software on a computer workstation, showed that all boutons of each cluster made synaptic contact with protrusions and branch points on a single dendrite. These contacts involved presynaptic dendrites (PSDs) in triadic arrangements. In contrast, the boutons-of-passage type terminations were generally characterized by contacts with PSDs, and some of the passing varicosities made simple such synaptic contacts. However, an intermediate termination pattern was also found in which boutons-of-passage fanned synaptic complexes with dendritic appendages involving PSD contacts.

    Postembedding immunogold-labeling techniques showed that the spinal and trigeminal terminals in Sm contained synaptic vesicle-associated glutamate, suggesting that glutamate is an excitatory neurotransmitter in these terminals. Corticothalamic tract terminals were also glutamatergic. Immunoreactivity to gamma-aminobutyric acid (GABA) was observed in PSDs originating from GABAergic intrinsic neurons and in axon tenninals supposed to originate from the reticular thalamic nucleus. A similar organization of glutamatergic and GABAergic elements was seen in the posterior thalamic region of owl monkeys.

    The different types of synaptic organization seen in Sm are consistent with the possibility that modality-selective nociceptive and thermoreceptive lamina I neurons terminate differentially in this nucleus and suggest a functional integration of cold and pain activity. The presentfindings provide evidence that such activity is transmitted by the excitatory amino acid glutamate and is modulated by inhibitory GABAergic mechanisms. Glutamate and GABA are also involved in the processing of ascending information in the posterior thalamic region of owl monkeys, showing that these substances are important for pain transmission in primates as well.

  • 8.
    Ericson, Ann-Charlott
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Öqvist, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sjöstrand, Sven-Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Morphological examination of the termination pattern of substance P-immunoreactive nerve fibers in human antral mucosa2002In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 107, no 1-3, p. 79-86Article in journal (Refereed)
    Abstract [en]

    The termination pattern of substance P (SP)-containing axons in human antral mucosa was examined using immunohistochemical techniques at the light and electron microscopic level. SP-immunoreactive (IR) axons were found to extend towards the pit region of the glands, where intraepithelial axons were observed. Electron microscopy showed immunostained axon profiles in close contact with the basement membrane of surface mucous cells. Membrane-to-membrane contacts between labeled axons and myofibroblast-like cells were identified, and SP-IR axons that were apposed to the epithelium were also in contact with subjacent myofibroblast-like cells. The anatomical relationship between SP-IR axons and the cells of the muscularis mucosae was investigated by light microscopy. Immunoreactivity for a-smooth muscle actin (a-sma) was used to visualize the smooth muscle cells, and the a-sma-IR cells were found to create a network that surrounded the gastric glands. Immunostained varicose axons ran alongside and in close apposition to the labeled muscle strands. Ultrastructural examination showed close contacts between SP-IR axon profiles and smooth muscle-like cells. In conclusion, SP-containing neurons may be important for sensory and secretomotor functions in the human antral mucosa.

  • 9.
    Ericson, Ann-Charlott
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nur, E Mohammed
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Petersson, F
    Karolinska University Hospital.
    Kechagias, Stergios
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    The Effects of Capsaicin on Gastrin Secretion in Isolated Human Antral Glands: Before and After Ingestion of Red Chilli2009In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 54, no 3, p. 491-498Article in journal (Refereed)
    Abstract [en]

    Background: Capsaicin is known to have regulatory effects on gastrointestinal functions via the vanilloid receptor (VR1). We reported previously that endocrine-like cells in the human antrum express VR1.

    Aim: To identify VR1-expressing endocrine-like cells in human antral glands and to examine whether stimulation with capsaicin causes release of gastrin, somatostatin, and serotonin. Further, to investigate the effects of a chilli-rich diet.

    Methods: Gastroscopic biopsies were received from 11 volunteers. Seven of the 11 subjects agreed to donor gastric biopsies a second time after a 3-week chilli-rich diet containing 1.4-4.2 mg capsaicin/day. VR1-immunoreactive cells were identified by double-staining immunohistochemistry against gastrin, somatostatin, and serotonin. For the stimulation studies, we used an in vitro method where antral glands in suspension were stimulated with 0.01 mM capsaicin and physiological buffer was added to the control vials. The concentrations of secreted hormones were detected and calculated with radioimmunoassay (RIA).

    Results: The light microscopic examination revealed that VR1 was localized in gastrin cells. The secretory studies showed an increase in release of gastrin and somatostatin compared to the control vials (P = 0.003; P = 0.013). Capsaicin-stimulation caused a consistent raise of the gastrin concentrations in the gland preparations from all subjects. A chilli-rich diet had an inhibitory effect on gastrin release upon stimulation compared to the results that were obtained before the start of the diet.

    Conclusion: This study shows that capsaicin stimulates gastrin secretion from isolated human antral glands, and that a chilli-rich diet decreases this secretion.

  • 10.
    Gerdin, Linda
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Surg Clin Jonkoping Cty, Sweden.
    Gonzalez-Castro, Ana M.
    Univ Autonoma Barcelona, Spain; Univ Autonoma Barcelona, Spain.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Persborn, Mats
    Surg Clin Jonkoping Cty, Sweden.
    Santos, Javier
    Univ Autonoma Barcelona, Spain; Univ Autonoma Barcelona, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain.
    Walter, Susanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Vicario, Maria
    Univ Autonoma Barcelona, Spain; Univ Autonoma Barcelona, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Nestle Res Soc Prod Nestle SA, Switzerland.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Acute psychological stress increases paracellular permeability and modulates immune activity in rectal mucosa of healthy volunteers2023In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 11, no 1, p. 31-41Article in journal (Refereed)
    Abstract [en]

    Background Psychological stress and increased permeability are implicated as contributing factors in the initiation and worsening of gastrointestinal diseases. A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported. Objective To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress-induced molecular events in the rectal mucosa under healthy conditions. Methods Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real-time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress. Results Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress-induced reduction in RNA expression of genes related to immune cell activation and maturation (CR2, CD20, TCLA1, BANK1, CD22, FDCSP), signaling molecules of homing of immune cells to the gut (chemokines: CCL21, CXCL13, and CCL19, and receptors: CCR7, CXCR5), and innate immunity (DUOX2). Eight of the 10 top down-regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with DUOX2 expression. Conclusion Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress-mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders.

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  • 11.
    Hamlin, Lina
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mackerlova, Ludmila
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Medicine and Health Sciences.
    AMPA-selective glutamate receptor subunits and their relation to glutamate-and GABA-like immunoreactive terminals in the nucleus submedius of the rat1996In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 217, no 2-3, p. 149-52Article in journal (Refereed)
    Abstract [en]

    Glutamate plays an important role in supraspinal nociceptive systems. Thus, glutamate is present in the nucleus submedius of the medial thalamus, a major relay for nociceptive information. In this study, immunoreactivity for the four subunits (GluR1-4) of alpha-amino-3-hydroxy-5-methyl-4-isoxasoleproprionate (AMPA) receptors was examined by a preembedding immunohistochemical method in order to evaluate the presence of this glutamate receptor subtype in the nucleus submedius. Combining the preembedding method with a postembedding immunogold technique, we found that AMPA receptor-like immunoreactivity was present postsynaptically to glutamatergic terminals but not to terminals containing gamma-aminobutyric acid (GABA). These findings suggest a role for AMPA receptors in excitatory synaptic transmission in the nucleus submedius of the rat thalamus.

  • 12.
    Kechagias, Stergios
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Botella, Sofia
    Petersson, Fredrik
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ericson, Ann-Charlott
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa2005In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 7, p. 775-782Article in journal (Refereed)
    Abstract [en]

    Objective. Capsaicin, which acts by binding to the vanilloid receptor-1 (VR1), has been shown to give protection against gastric mucosal injury and to enhance healing of gastric ulcers. Although VR1 has recently been reported to be present in non-neural tissues, it is primarily considered to be expressed in nociceptor sensory neurons of small diameter. The aim of the present study was to evaluate the distribution of VR1 immunoreactivity in the normal human gastric mucosa. Material and methods. Ten volunteers underwent gastroscopy and biopsies were obtained from the corpus and the antrum. The specimens were labelled immunohistochemically using polyclonal goat anti-VR1 and evaluated at the light- and electronmicroscopic level. Moreover, post-embedding immunogold labelling was performed and subsequently analysed at the electronmicroscopic level. Results. In the antrum, VR1 immunoreactivity was located in epithelial cells that fulfilled the criteria of endocrine cells of the "open type". These cells were located primarily in the neck region of the antral glands and the labelling was concentrated on the microvilli of these cells. At the ultrastructural level, round granulae with differences in electron density were identified in the basal compartment of the labelled cells. VR1 immunoreactivity was also identified in axon-like structures that were located in the lamina propria, often in close vicinity of vessels, in the corpus as well as in the antrum. Conclusions. VR1-immunoreactivity was evident in antral epithelial cells exhibiting characteristics of endocrine-like cells. This may indicate that the gastroprotective effects of capsaicin, which hitherto have been attributed to primary afferent neurons, at least partly may be explained by an action on specific epithelial cells in the antrum. © 2005 Taylor & Francis.

  • 13.
    Keita, Åsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Carlsson, A H.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Cigehn, M
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Mckay, D M:
    University of Calgary, Canada .
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats2013In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, no 6, p. e406-e417Article in journal (Refereed)
    Abstract [en]

    Background Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. Methods Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess 51chromium-edta (51Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP +/- anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. Key Results Stress increased 51Cr-edta and E.coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIPmast cellepithelial interactions in the regulation of barrier function. Conclusions andamp; Inferences Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterialepithelial interactions in stress-related intestinal disorders.

  • 14.
    Keita, Åsa V
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Gullberg, Elisabet
    Department of Pharmacy, Uppsala University, BMC, Uppsala, Sweden.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cellbiology. Linköping University, Faculty of Health Sciences.
    Salim, Sa’ad Y
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Kald, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Artursson, Per
    Department of Pharmacy, Uppsala University, BMC, Uppsala, Sweden.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum2006In: Laboratory investigation, ISSN 0023-6837, Vol. 86, no 5, p. 504-516Article in journal (Refereed)
    Abstract [en]

    The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal- and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial–epithelial cell interactions and delivery of antigens to the mucosal immune system.

  • 15.
    Keita, Åsa V
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Stress-induced barrier disruption of the follicle-associated epithelium involves corticotropin-releasing hormone, vasoactive intestinal peptide and mast cells2010In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 22, no 7, p. 770-e222Article in journal (Refereed)
    Abstract [en]

    Background The follicle-associated epithelium (FAE) is specialized in uptake and sampling of luminal antigens and bacteria. We previously showed that stress increased FAE permeability in rats. An increased uptake may alter antigen exposure in Peyers patches leading to intestinal disease. The aim of this study was to elucidate mechanisms involved in the acute stress-induced increase in FAE permeability. Methods Rats were pretreated i.p. with corticotropin-releasing hormone receptor (CRH-R) antagonist, neurokinin receptor 1 (NK-1R) antagonist, atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to 1-h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for measurements of permeability to 51Cr-EDTA, horseradish peroxidase (HRP) and chemically killed Escherichia coli K-12. Further, FAE segments were exposed in vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter- and receptor distribution was studied by immunohistochemistry. Key Results Stress-induced increases in uptake across FAE of HRP and E. coli were reduced by DOX, CRH-R antagonist and atropine, whereas the NK-1R antagonist decreased 51Cr-EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli passage, whereas SP increased bacterial and 51Cr-EDTA permeability. DOX counteracted all of these effects. Immunohistochemistry revealed CRH, acetylcholine, SP, and their receptors on mast cells within the Peyers patches, subepithelial dome, and adjacent villi. Conclusions & Inferences Corticotropin-releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress-related intestinal disorders.

  • 16.
    Mathus-Vliegen, Elisabeth
    et al.
    Univ Amsterdam, Netherlands.
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Weight loss with or without intragastric balloon causes divergent effects on ghrelin cell expression2021In: Obesity Science & Practice, E-ISSN 2055-2238, Vol. 7, no 2, p. 199-207Article in journal (Refereed)
    Abstract [en]

    Objective: The mechanism of action of intragastric balloons in the treatment of obesity is not fully understood. One of the hypotheses is that balloons might have an effect on the fundus, the area of ghrelin production. Methods: Participants were randomized to a 13-week period of sham or balloon treatment followed by a 13-week period of balloon therapy in everyone. Blood samples for ghrelin levels were taken in the fasting state and after a breakfast at the start, after 13 and 26 weeks. Biopsies for ghrelin cell immunohistochemistry were taken from the fundus at endoscopy. Results: Seven participants entered the balloon-balloon (BB) group and 11 the sham-balloon (SB) group. Despite a considerable weight loss, a median -17.9 kg (interquartile ranges -23.8 to -0.5) in the BB group and -18.3 kg (-22.7 to -14.7) in the SB group, fasting ghrelin and meal-induced ghrelin response did not change. In the SB group, the number of ghrelin cells increased significantly (p 0.001) from 110.6 (83.6-118.9) to 160.2 (128.5-223.0) while on sham treatment and returned to initial levels, 116.3 (91.7-146.9) (p 0.001), when they received their first balloon. No significant changes in ghrelin cell numbers were observed in the BB group. Conclusion: In participants without a balloon, weight loss induced an increase in ghrelin cell numbers in the fundus, which was annulled by the subsequent placement of a balloon. The effect of a balloon might be explained by effects on ghrelin cell numbers or ghrelin cell activity.

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  • 17.
    Metcalf, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Berg, Anna
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Lisander, Björn
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Nitric oxide does not cause extravasation in endotoxemic rats2005In: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 58, no 5, p. 1047-1054Article in journal (Refereed)
    Abstract [en]

    Background: Nitric oxide (NO) formed from inducible NO synthase (iNOS) is assumed to promote vascular permeability in sepsis and endotoxemia.

    Methods: Thirty-seven anesthetized rats were examined for the effects of endotoxin. After randomization, 17 animals had lipopolysaccharide (LPS) administered and 20 rats served as controls and were given the corresponding volume of saline. The observation period was 5 hours after administration of endotoxin. Mean arterial blood pressure, heart rate, and hematocrit were recorded in all animals, and transcapillary exchange of albumin, tissue water content, immunohistochemistry for nitric oxide synthase, and blood gases were investigated in subsets of animals.

    Results: When anesthetized rats were studied for 5 hours after endotoxin (LPS), the sequestration of albumin decreased in the intestine (double-isotope method) and there was no increased water content (freeze-drying technique) when the elevated tissue plasma volume of the LPS-treated rats was corrected for. Immunohistochemical methods showed a similar distribution and intensity of staining for endothelial NOS and neuronal NOS in LPS and control groups. In the lung of the LPS-treated rats, there was a significantly larger number of infiltrating, inflammatory cells staining for iNOS. There was no iNOS demonstrated in vascular structures or heart.

    Conclusion: At 5 hours after LPS, there was no increased loss of water or albumin from the circulation. This challenges the notion that NO causes vascular damage in endotoxemia and extravasation as an obligatory sequela to endotoxemia.

  • 18.
    Velin Keita, Åsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Braaf, Ylva
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Increased antigen and bacterial uptake in follicle-associated epithelium induced by chronic psychological stress in rats2004In: Gut, ISSN 0017-5749, Vol. 53, no 4, p. 494-500Article in journal (Refereed)
    Abstract [en]

    Background: Chronic stress affects the course of inflammatory bowel disease and experimental colitis, and may also initiate intestinal inflammation in rats.

    Aim: To investigate the effects of stress on the M cell containing follicle associated epithelium, specialised in antigen uptake.

    Subjects and methods: Wistar rats were submitted to acute water avoidance stress for one hour or chronic water avoidance stress for 1 hour/day for 10 consecutive days. Permeability to 51Cr-EDTA, horseradish peroxidase, and chemically killed Escherichia coli K-12 was studied in both villus and follicle associated epithelium in Ussing chambers. Segments were further examined by light, electron, and confocal microscopy.

    Results: Acute stress increased horseradish peroxidase flux in villus as well as in follicle associated epithelium. Chronic stress further increased permeability to horseradish peroxidase in villus and follicle associated epithelium, in the latter by almost fourfold. Moreover, chronic stress induced over 30 times increased E coli passage in follicle associated epithelium whereas there was no significant increase in villus epithelium. Bacterial uptake was confirmed by confocal microscopy showing fluorescent bacteria penetrating and passing through the epithelial surface.

    Conclusions: These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer’s patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa.

  • 19.
    Wallon, Conny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Persborn, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Wang, Arthur
    University of Calgary.
    Phan, Van
    University of Calgary.
    Lampinen, Maria
    Uppsala University.
    Vicario, Maria
    CIBERehd.
    Santos, Javier
    CIBERehd.
    Sherman, Philip M
    University of Toronto.
    Carlson, Marie
    Uppsala University.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    McKay, Derek M
    University of Calgary.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, no 5, p. 1597-1607Article in journal (Refereed)
    Abstract [en]

    BACKGROUND andamp; AIMS: Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropinreleasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. METHODS: Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers (51Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). RESULTS: Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), alpha-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. CONCLUSIONS: We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation.

  • 20.
    Wallon, Conny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Yang, P.
    Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    McKay, D. M.
    Department of Physiology and Biophysics, University of Calgary, Canada.
    Sherman, P. M.
    Departments of Paediatrics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
    Perdue, M. H.
    Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    Objective: Persistent stress and life events affect the course of ulcerativecolitis and irritable bowel syndrome by largely unknown mechanisms.Corticotropin-releasing hormone (CRH) has been implicated asan important mediator of stress-induced abnormalities in intestinalmucosal function in animal models, but to date no studies inhuman colon have been reported. The aim was to examine the effectsof CRH on mucosal barrier function in the human colon and toelucidate the mechanisms involved in CRH-induced hyper-permeability.

    Design: Biopsies from 39 volunteers were assessed for macromolecularpermeability (horseradish peroxidise (HRP), 51Cr-EDTA), andelectrophysiology after CRH challenge in Ussing chambers. Thebiopsies were examined by electron and confocal microscopy forHRP and CRH receptor localisation, respectively. Moreover, CRHreceptor mRNA and protein expression were examined in the humanmast cell line, HMC-1.

    Results: Mucosal permeability to HRP was increased by CRH (2.8±0.5pmol/cm2/h) compared to vehicle exposure (1.5±0.4 pmol/cm2/h),p = 0.032, whereas permeability to 51Cr-EDTA and transmucosalelectrical resistance were unchanged. The increased permeabilityto HRP was abolished by -helical CRH (9-41) (1.3±0.6pmol/cm2/h) and the mast cell stabiliser, lodoxamide (1.6±0.6pmol/cm2/h). Electron microscopy showed transcellular passageof HRP through colonocytes. CRH receptor subtypes R1 and R2were detected in the HMC-1 cell line and in lamina propria mastcells in human colon.

    Conclusions: Our results suggest that CRH mediates transcellular uptake ofHRP in human colonic mucosa via CRH receptor subtypes R1 andR2 on subepithelial mast cells. CRH-induced macromolecular uptakein human colon mucosa may have implications for stress-relatedintestinal disorders.

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