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Ericson, Ann-Charlott
Publications (10 of 18) Show all publications
Keita, Å., Carlsson, A. H., Cigehn, M., Ericson, A.-C., Mckay, D. M. & Söderholm, J. D. (2013). Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats. Neurogastroenterology and Motility, 25(6), e406-e417
Open this publication in new window or tab >>Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats
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2013 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, no 6, p. e406-e417Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keywords
Inflammatory bowel disease, permeability, Peyers patch, Ussing chamber
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-94315 (URN)10.1111/nmo.12127 (DOI)000318945400005 ()
Note

Funding Agencies|Swedish Research Council|K2012-55X-12618-16-3|

Available from: 2013-06-24 Created: 2013-06-24 Last updated: 2017-12-06
Wallon, C., Persborn, M., Jönsson, M., Wang, A., Phan, V., Lampinen, M., . . . Söderholm, J. D. (2011). Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis. Gastroenterology, 140(5), 1597-1607
Open this publication in new window or tab >>Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis
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2011 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, no 5, p. 1597-1607Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier Science B.V. Amsterdam, 2011
Keywords
Intestinal Permeability, Inflammatory Bowel Disease, Immune Response, Stress
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68223 (URN)10.1053/j.gastro.2011.01.042 (DOI)000290028200040 ()
Available from: 2011-05-13 Created: 2011-05-13 Last updated: 2017-12-11
Keita, Å. V., Söderholm, J. D. & Ericson, A.-C. (2010). Stress-induced barrier disruption of the follicle-associated epithelium involves corticotropin-releasing hormone, vasoactive intestinal peptide and mast cells. Neurogastroenterology and Motility, 22(7), 770-e222
Open this publication in new window or tab >>Stress-induced barrier disruption of the follicle-associated epithelium involves corticotropin-releasing hormone, vasoactive intestinal peptide and mast cells
2010 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 22, no 7, p. 770-e222Article in journal (Refereed) Published
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.

Keywords
inflammatory bowel disease; neurotrans-mitter; permeability; Peyers patches; Ussing chamber
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14565 (URN)10.1111/j.1365-2982.2010.01471.x (DOI)000278525200009 ()
Available from: 2007-07-03 Created: 2007-07-03 Last updated: 2017-12-13
Ericson, A.-C., Nur, E. M., Petersson, F. & Kechagias, S. (2009). The Effects of Capsaicin on Gastrin Secretion in Isolated Human Antral Glands: Before and After Ingestion of Red Chilli. Digestive Diseases and Sciences, 54(3), 491-498
Open this publication in new window or tab >>The Effects of Capsaicin on Gastrin Secretion in Isolated Human Antral Glands: Before and After Ingestion of Red Chilli
2009 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 54, no 3, p. 491-498Article in journal (Refereed) Published
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.

Keywords
Capsaicin, Gastrin cells, Gastric hormone-release, Immunohistochemistry, Radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16872 (URN)10.1007/s10620-008-0400-1 (DOI)
Available from: 2009-02-22 Created: 2009-02-20 Last updated: 2017-12-13
Wallon, C., Yang, P., Keita, Å., Ericson, A.-C., McKay, D. M., Sherman, P. M., . . . Söderholm, J. D. (2008). Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut, 57(1), 50-58
Open this publication in new window or tab >>Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro
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2008 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no 1, p. 50-58Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
London UK: BMJ Group, 2008
Keywords
CRH receptor subtypes, barrier function, electron microscopy, human mast cell line, intestinal mucosa
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13153 (URN)10.1136/gut.2006.117549 (DOI)000251778400013 ()
Available from: 2008-04-07 Created: 2008-04-07 Last updated: 2017-12-13Bibliographically approved
Berg, A., Redéen, S., Sjöstrand, S.-E. & Ericson, A.-C. (2007). Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands. Digestive Diseases and Sciences, 52(1), 126-136
Open this publication in new window or tab >>Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands
2007 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 52, no 1, p. 126-136Article in journal (Refereed) Published
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-40472 (URN)10.1007/s10620-006-9439-z (DOI)53339 (Local ID)53339 (Archive number)53339 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
Keita, Å. V., Gullberg, E., Ericson, A.-C., Salim, S. Y., Wallon, C., Kald, A., . . . Söderholm, J. D. (2006). Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum. Laboratory investigation, 86(5), 504-516
Open this publication in new window or tab >>Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum
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2006 (English)In: Laboratory investigation, ISSN 0023-6837, Vol. 86, no 5, p. 504-516Article in journal (Refereed) Published
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.

Keywords
E. coli, horseradish peroxidase, M cell, permeability, Peyer's patches
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14563 (URN)10.1038/labinvest.3700397 (DOI)
Available from: 2007-07-03 Created: 2007-07-03
Kechagias, S., Botella, S., Petersson, F., Borch, K. & Ericson, A.-C. (2005). Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa. Scandinavian Journal of Gastroenterology, 40(7), 775-782
Open this publication in new window or tab >>Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa
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2005 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 7, p. 775-782Article in journal (Refereed) Published
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31189 (URN)10.1080/00365520510015782 (DOI)16930 (Local ID)16930 (Archive number)16930 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
Metcalf, K., Berg, A., Ericson, A.-C. & Lisander, B. (2005). Nitric oxide does not cause extravasation in endotoxemic rats. Journal of Trauma, 58(5), 1047-1054
Open this publication in new window or tab >>Nitric oxide does not cause extravasation in endotoxemic rats
2005 (English)In: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 58, no 5, p. 1047-1054Article in journal (Refereed) Published
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.

Keywords
albumin, endotoxin, immunohistochemistry, lipopolysaccharide, nitric oxide, nitric oxide synthase, rats, tissue plasma clearance, water
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31547 (URN)10.1097/01.ta.0000171988.56193.a6 (DOI)17348 (Local ID)17348 (Archive number)17348 (OAI)
Note

On the day of the defence day the status of this article was a manuscript.

Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
Berg, A., Redéen, S., Grenegård, M., Ericson, A.-C. & Sjöstrand, S.-E. (2005). Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands. American Journal of Physiology - Gastrointestinal and Liver Physiology, 289(6), G1061-G1066
Open this publication in new window or tab >>Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands
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2005 (English)In: 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) Published
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31485 (URN)10.1152/ajpgi.00230.2005 (DOI)17277 (Local ID)17277 (Archive number)17277 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
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