Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of gamma-aminobutyric acid (GABA) to antral mucosal fragments in short-term incubation results in dose-dependent and bicuculline-sensitive stimulation of gastrin release and inhibition of somatostatin release, respectively. These effects of GABA on antral gastrin and somatostatin release closely resembled the actions of cholinergic agonists on G- and D-cell function. The present study examines the possibility that the effects of GABA on antral peptide release may be mediated, in part, through stimulation of antral cholinergic neurons. Inclusion of either atropine or pirenzepine in incubation medium prevented GABA-induced stimulation of gastrin release and inhibition of somatostatin release. Addition of the acetylcholinesterase inhibitor, physostigmine, caused a leftward shift in the GABA dose-response curve and increased by 10-fold the sensitivity of the antral preparation to GABA stimulation. Studies with tetrodotoxin suggest that GABA-stimulated gastrin release is mediated through activation of neurons contained within the antral mucosal/submucosal fragments. Hexamethonium, the ganglionic nicotinic receptor antagonist, did not affect GABA-induced gastrin release. These results indicate that GABA affects antral gastrin and somatostatin release through stimulation of antral postganglionic cholinergic neurons.
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PMID:Cholinergic mediation of gamma-aminobutyric acid-induced gastrin and somatostatin release from rat antrum. 287 17

The patterns of somatostatin secretion from the fundus, the main source of somatostatin, and the antrum, the site of paracrine regulation of gastrin secretion, were examined using perifused antral and fundic segments from rat stomach. Gastrin secretion fundic segments from rat stomach. Gastrin secretion could be obtained from antral segments only. Somatostatin secretion was obtained from both antral and fundic segments. 1,1-Dimethyl-4-phenylpiperazinium (DMPP) (10(-5) and 10(-4) M) and bombesin-14 (10(-8) and 10(-6) M) caused concentration-dependent increases in somatostatin secretion that were of the same magnitude in antral and fundic segments. These increases were also of the same magnitude as those obtained in the vascularly perfused whole stomach. Atropine (3 X 10(-7) M) inhibited the somatostatin response to DMPP (10(-4) M) to the same extent in antral (50 +/- 12% inhibition) and fundic (55 +/- 12% inhibition) segments. Hexamethonium (10(-5) M) also inhibited the response to DMPP to the same extent in antral (80 +/- 9%) and fundic (78 +/- 19%) segments. Methacholine caused a typically muscarinic decrease in somatostatin secretion that was of the same magnitude in antral (27 +/- 6%) and fundic (25 +/- 6%) segments. The identical patterns of somatostatin secretion from the two regions of the stomach imply that somatostatin secretion measured in the vascularly perfused whole stomach is a valid reflection of somatostatin secretion by the antrum.
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PMID:Identical patterns of somatostatin secretion from isolated antrum and fundus of rat stomach. 289 24

In cats electrical vagal stimulation leads to an atropine-resistant release of gastrin. Hexamethonium on the other hand blocks the release response. These data suggest that at least one noncholinergic and one cholinergic neuron are involved in the vagal pathway innervating the gastrin producing cells. Exogenously administrated somatostatin also inhibits the vagally induced release of gastrin. Vagal stimulation decreases the levels of somatostatin in portal blood, suggesting that a release of gastric somatostatin, occurring during basal conditions, is inhibited. It is therefore possible that the vagally induced release of gastrin is in part secondary to the decreased somatostatin secretion. In contrast, electrical stimulation stimulates the release of gastrin as well as that of somatostatin into the antral lumen. However, the intraluminal release of these peptides only occurs in the presence of low antral pH. In rats, low doses of atropine (0.05 mg/kg) completely inhibits the intragastric vagally mediated release of somatostatin, which leads to an approximately 10-fold enhancement of the simultaneously occurring gastrin release. The intraluminally released somatostatin most likely derives from pH sensitive antral D cells of the open type. The vagal innervation of this population of somatostatin producing cells appears to be cholinergic. Activation of the sympathetic nervous system inhibits the vagally induced release of gastrin dependently of the prevailing antral pH. This inhibitory effect is probably exerted by a neurogenic mechanism at the ganglionic level. In contrast, basal gastrin release is enhanced by activation by the sympathoadrenal system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurogenic control of release of gastrin and somatostatin. 614 89

This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK8) and gastrin 17 (G17)act on motor functions of the intact canine gastrointestinal tract. In the antrum, studies of tachyphylaxis and effects of antagonists showed that i.a. G17 acted through CCKB receptors to activate contractions, whereas CCK8 acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical field-stimulated contractions, apparently by release of nitric oxide [blocked by N-nitro-L-arginine (L-NNA) or NG-L-arginine methyl ester]. These inhibitory effects were abolished by YM022 (a CCKB antagonist) but not by L-364, 718 (a CCKA antagonist). However, i.a. CCK8 increased electrical field-stimulated contractions and L-364, 718 reversed this effect. In isolated perfused segments of distal intestine, CCK8 caused inhibition and excitation and released vasoactive intestinal peptide (VIP) into the venous effluent. CCK tetrapeptide and G17 had inconsistent effects. Excitation and VIP release were inhibited by L-364, 718. L-NNA potentiated excitatory responses and abolished inhibitory responses. Tetrodotoxin and atropine abolished and hexamethonium reduced excitatory responses to CCK8, but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK8 still enhanced it. L-364, 718 abolished hexamethonium-resistant contractions and VIP release. Thus, CCK/gastrin peptides act on neural receptors in intact canine gastrointestinal tract. In antrum, activation of neural CCKA or CCKB receptors initiates contractions. In intestine, CCKA receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCKB receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.
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PMID:Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: role of vasoactive intestinal peptide and nitric oxide. 885 8