Inhibition of gastric acid secretion in rat stomach by PACAP is mediated by secretin, somatostatin, and PGE2

2000 ◽  
Vol 278 (1) ◽  
pp. G121-G127 ◽  
Author(s):  
P. Li ◽  
T.-M. Chang ◽  
D. Coy ◽  
W. Y. Chey
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Digestive System ◽  
Regulatory Mechanism ◽  
Inhibitory Effect ◽  
Inhibitory Mechanism ◽  
Rat Stomach ◽  
Pituitary Adenylate Cyclase ◽  
Local Release

Pituitary adenylate cyclase-activating polypeptide (PACAP), existing in two variants, PACAP-27 and PACAP-38, is found in the enteric nervous system and regulates function of the digestive system. However, the regulatory mechanism of PACAP on gastric acid secretion has not been well elucidated. We investigated the inhibitory action of PACAP-27 on acid secretion and its mechanism in isolated vascularly perfused rat stomach. PACAP-27 in four graded doses (5, 10, 20, and 50 μg/h) was vascularly infused to determine its effect on basal and pentagastrin (50 ng/h)-stimulated acid secretion. To study the inhibitory mechanism of PACAP-27 on acid secretion, a rabbit antisecretin serum, antisomatostatin serum, or indomethacin was administered. Concentrations of secretin, somatostatin, PGE2, and histamine in portal venous effluent were measured by RIA. PACAP-27 dose-dependently inhibited both basal and pentagastrin-stimulated acid secretion. PACAP-27 at 10 μg/h significantly increased concentrations of secretin, somatostatin, and PGE2 in basal or pentagastrin-stimulated state. The inhibitory effect of PACAP-27 on pentagastrin-stimulated acid secretion was reversed 33% by an antisecretin serum, 80.0% by an antisomatostatin serum, and 46.1% by indomethacin. The antisecretin serum partially reduced PACAP-27-induced local release of somatostatin and PGE2. PACAP-27 at 10 μg/h elevated histamine level in portal venous effluent, which was further increased by antisomatostatin serum. However, antisomatostatin serum did not significantly increase acid secretion. It is concluded that PACAP-27 inhibits both basal and pentagastrin-stimulated gastric acid secretion. The effect of PACAP-27 is mediated by local release of secretin, somatostatin, and PGE2 in isolated perfused rat stomach. The increase in somatostatin and PGE2 levels in portal venous effluent is, in part, attributable to local action of the endogenous secretin.

PACAP stimulates gastric acid secretion in the rat by inducing histamine release

2001 ◽  
Vol 281 (4) ◽  
pp. G997-G1003 ◽  
Author(s):  
Arne K. Sandvik ◽  
Guanglin Cui ◽  
Ingunn Bakke ◽  
Bjørn Munkvold ◽  
Helge L. Waldum
Keyword(s):  
Acid Secretion ◽  
Histamine Release ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Rat Stomach ◽  
Neurohumoral Regulation ◽  
Ecl Cell ◽  
Pituitary Adenylate Cyclase ◽  
Awake Rat

Previous studies have shown that pituitary adenylate cyclase-activating peptide (PACAP) stimulates enterochromaffin-like (ECL) cell histamine release, but its role in the regulation of gastric acid secretion is disputed. This work examines the effect of PACAP-38 on aminopyrine uptake in enriched rat parietal cells and on histamine release and acid secretion in the isolated vascularly perfused rat stomach and the role of PACAP in vagally (2-deoxyglucose) stimulated acid secretion in the awake rat. PACAP has no direct effect on the isolated parietal cell as assessed by aminopyrine uptake. PACAP induces a concentration-dependent histamine release and acid secretion in the isolated stomach, and its effect on histamine release is additive to gastrin. The histamine H2antagonist ranitidine potently inhibits PACAP-stimulated acid secretion without affecting histamine release. Vagally stimulated acid secretion is partially inhibited by a PACAP antagonist. The results from the present study strongly suggest that PACAP plays an important role in the neurohumoral regulation of gastric acid secretion. Its effect seems to be mediated by the release of ECL cell histamine.

Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach

1981 ◽  
Vol 240 (3) ◽  
pp. E274-E278
Author(s):  
Y. Goto ◽  
M. Berelowitz ◽  
L. A. Frohman
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Rat Stomach ◽  
Beta Adrenergic ◽  
Somatostatin Secretion ◽  
Adrenergic Mechanism ◽  
Dose Dependent

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.

scholarly journals Regulatory mechanism of gastric acid secretion and mucosal integrity. An analysis with various gene deficient mice.

2002 ◽  
Vol 120 (3) ◽  
pp. 159-171 ◽  
Author(s):  
Susumu OKABE ◽  
Kazuharu FURUTANI ◽  
Kazuhiko MAEDA ◽  
Takeshi AIHARA ◽  
Teruaki FUJISHITA ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Regulatory Mechanism ◽  
Mucosal Integrity ◽  
Deficient Mice

Pentagastrin-stimulated gastric acid secretion by the isolated perfused rat stomach

Life Sciences ◽  
1984 ◽  
Vol 34 (25) ◽  
pp. 2515-2523 ◽  
Author(s):  
Glenn M. Short ◽  
M.Michael Wolfe ◽  
James E. McGuigan
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Rat Stomach

Stimulation of neurons in rat ARC inhibits gastric acid secretion via hypothalamic CRF1/2- and NPY-Y1 receptors

2003 ◽  
Vol 285 (6) ◽  
pp. G1075-G1083 ◽  
Author(s):  
Johannes J. Tebbe ◽  
Silke Mronga ◽  
Martin K.-H. Schäfer ◽  
Jens Rüter ◽  
Peter Kobelt ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Receptor Antagonist ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Excitatory Amino Acid ◽  
Inhibitory Effect ◽  
Receptor Subtypes ◽  
Npy Receptor ◽  
Y1 Receptors ◽  
Open Question

Neuropeptide Y (NPY) neuronal projections from the arcuate nucleus (ARC) have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus (PVN) as part of the ARC-PVN axis. The existence of a positive feedback loop involving CRF receptors in the PVN has been suggested. Exogenous NPY and CRF in the PVN have been shown to inhibit gastric acid secretion. Recently, we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via vagal pathways. To what extent NPY- and CRF-mediated mechanisms in the PVN contribute to the CNS modulation of gastric acid secretion is still an open question. In the present study, we performed consecutive bilateral microinjections of antagonists to NPY receptor subtypes Y1 and Y2 and to CRF1/2 receptors in the PVN and of the excitatory amino acid kainate in the ARC to assess the role of NPY- and CRF-mediated mechanisms in the kainate-induced effects on gastric acid secretion. Gastric acid secretion was measured at the basal condition and during pentagastrin (16 μg/kg body wt) stimulation. Microinjection of vehicle in the PVN and kainate in the ARC decreased gastric acid secretion. Microinjection of the specific NPY-Y1 receptor antagonist BIBP-3226 (200 pmol) and the nonspecific CRF1/2 antagonist astressin (30 pmol) in the PVN abolished the inhibitory effect of neuronal activation in the ARC by kainate on gastric acid secretion. The CRF antagonist astressin was more effective. Pretreatment with the NPY-Y2 receptor antagonist BIIE-0246 (120 pmol) in the PVN had no significant effect. Our results indicate that activation of neurons in the ARC inhibits gastric acid secretion via CRF1/2 and NPY-Y1 receptor-mediated pathways in the PVN.

Cholecystokinin inhibits gastric acid secretion through type "A" cholecystokinin receptors and somatostatin in rats

1992 ◽  
Vol 263 (3) ◽  
pp. G287-G292 ◽  
Author(s):  
K. C. Lloyd ◽  
H. E. Raybould ◽  
J. H. Walsh
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Type A ◽  
Inhibitory Effect ◽  
Cck Receptors ◽  
Cholecystokinin Receptors ◽  
Maximum Inhibition ◽  
Vagal Reflex ◽  
Dependent Pathway

The purpose of this study was to determine whether selective antagonism of type "A" cholecystokinin (CCK) receptors blocks inhibition of gastric acid secretion produced by CCK and whether this inhibition is mediated through either a somatostatin-dependent pathway or a vago-vagal reflex. Intravenous infusion of CCK (0.04-10 nmol.kg-1.h-1) dose dependently inhibited pentagastrin-stimulated gastric acid secretion in urethan-anesthetized rats, with a 50% inhibitory dose of 0.9 nmol.kg-1.h-1 and a maximum inhibition of approximately 50%. Blockade of type A CCK receptors using the selective type A receptor antagonist MK-329 completely reversed the inhibitory effect produced by a maximal dose (4 nmol.kg-1.h-1) of CCK. Immunoneutralization of endogenous somatostatin by administration of somatostatin monoclonal antibody abolished the inhibition produced by CCK. Concentrations of somatostatin in portal venous plasma were significantly increased after CCK administration; the increase in somatostatin was blocked by pretreatment with MK-329. In contrast, CCK-induced inhibition of gastric acid secretion was unaltered after perivagal capsaicin treatment. These results indicate that CCK inhibits gastric acid secretion in rats by activation of type A CCK receptors and through release of endogenous somatostatin.

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