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In vitro studies on cholecystokinin-induced inhibition of acid formation in gastric glands
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The design of methods useful for the preparation of viable glands and cells from the gastric mucosa allowed detailed studies on the mechanisms that regulate gastric acid secretion. The preparation of rabbit gastric glands was the first suitable method to be used and a number of important scientific contributions have been accomplished with this method. Using this method we studied the effect of CCK-like peptides on [14C]aminopyrine accumulation stimulated by histamine, in order to fmd out whether such peptides can inhibit the production of acid in the parietal cell. We also developed a method for the study of viable rat gastric glands that allowed comparative studies in the rat species.

In rabbit gastric glands CCK-like pep tides inhibited histamine stimulated acid formation whereas gastrin peptides were ineffective. The most potent and efficacious peptides were CCK 8 and the cholecystokinetic amphibian decapeptide cemlein reducing the maximal histamine stimulation of aminopyrine accumulation by 35-38%. The concentration of peptide necessary for eliciting inhibition was in the range of that reported to stimulate amylase secretion in similar in vitro experiments on isolated pancreatic acini, representing a well established physiological function of CCK. Analyses of somatostatin content in the incubation medium revealed that biologically active concentrations of endogenous somatostatin were released into the incubation medium. The rate of somatostatin release increased after CCK 8 or cemlein was added, whereas with G 17, the concentration of somatostatin remained unchanged. In further experiments performed with rabbit mucosal cells prepared from the gastric glands, it was demonstrated that the inhibitory property of CCK 8 only was apparent if a sufficient amount of endocrine cells were present during incubation. In highly purified fractions of parietal cells, however, a small stimulatory effect appeared, a finding that is consistent with similar capacity of gastrin and CCK stimulating the CCK2 receptors present on the parietal cell.

A method useful for the study of rat gastric glands was developed. The viability of the rat gastric glands appeared excellent as judged by morphological characterisation and functional assessment by means of [14C]aminopyrine accumulation. Upon stimulation with a high dose of histamine the production of acid increased 5-fold over basal. Pentagastrin and CCK 8 were ineffective stimulators per se, but in combination with histamine a marked potentiation occurred. Somatostatin effectively inhibited histamine-stimulated acid formation both in rabbit and rat gastric glands.

In conclusion, CCK-like peptides inhibit histamine stimulated acid formation in gastric glands prepared from rabbit. The inhibition is mediated in a paracrine-like mode via the release of endogenous somatostatin. A method useful for the study of viable rat gastric glands was developed. In contrast to rabbit gastric glands, CCK 8 potentiated histamine stimulation in rat glands.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2000. , 51 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 639
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25629Local ID: 10000ISBN: 91-7219-740-4 (print)OAI: oai:DiVA.org:liu-25629DiVA: diva2:246177
Public defence
2000-11-13, Berzeliussalen, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-14Bibliographically approved
List of papers
1. Cholecystokinin and Gastrin Inhibit Histamine Stimulated Aminopyrine Uptake in Isolated Rabbit Gastric Glands
Open this publication in new window or tab >>Cholecystokinin and Gastrin Inhibit Histamine Stimulated Aminopyrine Uptake in Isolated Rabbit Gastric Glands
1989 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 94, no 2, 111-122 p.Article in journal (Refereed) Published
Abstract [en]

In the present study we have analyzed if cholecystokinin (CCK) or gastrin (G) can inhibit acid production in isolated rabbit gastric glands as revealed by the aminopyrine technique.

The results show that G 17 I, CCK 8 NS, CCK 8 S, ceruletide and CCK 39 significantly inhibit histamine induced aminopyrine accumulation. No significant inhibition was noted for G 4, G 34 and NT G 1–13. As a group the CCK peptides were more effective than the gastrin peptides in inhibiting the aminopyrine uptake. CCK 8 S and ceruletide, the most potent inhibitors, reduced histamine induced aminopyrine accumulation with an ED50 of 10−9 and 10−10 M respectively. These potencies are similar to those by which CCK peptides stimulate isolated pancreatic acini to secrete amylase. Inhibition evoked by CCK 8 S was most effective following 20–40 min of incubation time, possibly indicating that the effect is mediated by the release of an intermediate substance.

The results may therefore indicate a role for cholecystokinin as a physiological inhibitor of acid secretion in the rabbit. The results may also contribute to explain why the potent gastric secretagogue gastrin per se fails to stimulate acid formation in gastric glands isolated from the rabbit.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79779 (URN)10.3109/03009738909178556 (DOI)
Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2017-12-07Bibliographically approved
2. Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands
Open this publication in new window or tab >>Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands
1989 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 419, 765-774 p.Article in journal (Refereed) Published
Abstract [en]

1. The purpose of the present study was to investigate the role of somatostatin in the inhibition of acid production induced by caerulein and cholecystokinin (CCK) in isolated rabbit gastric glands. Acid production was estimated by the aminopyrine technique.

2. Exogenous somatostatin 14 and somatostatin 28 (10(-7) M) reduced to a similar extent the aminopyrine uptake produced by 5 x 10(-5) M-histamine during the course of 40 min incubation.

3. Significant inhibition of histamine-stimulated aminopyrine accumulation occurred at a somatostatin 14 concentration of 10(-9) M.

4. Caerulein and CCK octapeptide (10(-13)-10(-7) M) were found to release somatostatin from isolated gastric glands in a dose-dependent manner. The dose-response relationships for somatostatin release and inhibition of aminopyrine uptake were similar. Thus, the half-maximal dose approximations for somatostatin release and inhibition of aminopyrine uptake were 0.5 and 1.4 x 10(-9) M respectively for CCK octapeptide and 0.9 and 2.5 x 10(-11) M for caerulein. Heptadecapeptide gastrin proved to be a very poor releaser of somatostatin in the system used. The CCK octapeptide-induced somatostatin release was time dependent and the concentrations of somatostatin that accumulated in the incubation medium were similar to those of exogenous somatostatin that were needed to evoke inhibition.

5. The present results support the concept that cholecystokinin inhibits gastric acid secretion by releasing somatostatin from endocrine-like cells in the gastric mucosa. It is suggested that cholecystokinin-related peptides may play a physiological role in inhibiting gastric acid secretion. A similar role for gastrin is not supported by the present study.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79780 (URN)2576071 (PubMedID)
Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2017-12-07Bibliographically approved
3. Characterization of oxyntic glands isolated from the rat gastric mucosa
Open this publication in new window or tab >>Characterization of oxyntic glands isolated from the rat gastric mucosa
Show others...
2001 (English)In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 128, no 2, 349-357 p.Article in journal (Refereed) Published
Abstract [en]

A simple and reproducible method for isolating oxyntic glands from the rat gastric mucosa was developed. The mucosa was incubated with pronase and EGTA, and then treated mechanically to release glands that were separated from single cells by sedimentation. Parietal cells were identified by immunostaining using a monoclonal antibody against H,K-ATPase. The glandular cells appeared morphologically intact. By careful control of the conditions of gland isolation, long glandular structures comprising hundreds of cells surrounding the lumen were obtained. Intraperitoneal injection of Br-deoxyuridine in the rat 1.5 h before the isolation procedure resulted in glands with a labeling of cells in their neck region. The glands were viable, as demonstrated by their ability to respond to various hormones. Histamine dose-dependently stimulated the acid formation which was measured as the accumulation of [14C]aminopyrine. At 100 microM histamine the accumulation was increased 5-10-fold. At 100 nM, pentagastrin potentiated the histamine stimulated accumulation by approximately 40% but pentagastrin alone did not stimulate. The oxyntic glands obtained by the present procedure appear useful for studies on cell physiology, including regulation of acid secretion, cellular interactions, and possibly also differentiation and proliferation mechanisms since long glandular fragments that contained the proliferative zone could be isolated.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24920 (URN)10.1016/S1095-6433(00)00309-3 (DOI)11223396 (PubMedID)9324 (Local ID)9324 (Archive number)9324 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
4. Effects of cholecystokinin on acid formation in glands and cells isolated from rabbit and rat gastric mucosa
Open this publication in new window or tab >>Effects of cholecystokinin on acid formation in glands and cells isolated from rabbit and rat gastric mucosa
Show others...
2000 (English)In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 126, no 1, 77-84 p.Article in journal (Refereed) Published
Abstract [en]

Isolated gastric glands and isolated cells prepared from rabbit and rat were studied to analyse the influence of cholecystokinin octapeptide (CCK 8) on histamine stimulated parietal cell acid formation as assessed by [14C]aminopyrine sequestered in acid tissue compartments. In rabbit gastric glands, CCK 8 evoked 32±6% (P<0.01) inhibition of histamine stimulated acid formation, whereas in glands prepared from rat no inhibition was recorded. Instead, CCK 8 seemed to induce a variable increase of the histamine stimulation in rat gastric glands as the aminopyrine accumulation was increased by 110±46% (P<0.1). Further studies on cell preparations derived from rabbit gastric mucosa revealed dual properties of CCK 8, eliciting either inhibition or stimulation of the parietal cell depending on the presence of endocrine cells. The results show that paracrine communication may be effective in glandular preparations, but seems to vary depending on species.

Keyword
Inhibition of acid, Acid secretion, Fundic glands, In vitro, Paracrine function, Parietal cells, Histamine stimulation, Somatostatin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24925 (URN)10.1016/S1095-6433(00)00188-4 (DOI)10908854 (PubMedID)9330 (Local ID)9330 (Archive number)9330 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved

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