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)

Chicken antrum was found to contain 7 nmol/g of carboxyamidated gastrin/CCK-like peptides. The predominant chicken gastrin (so named due to the antral origin) contained 53 amino acid residues: DWPEPPSQEQ QQRFISRFLP HVFAELSDRK GFVQGNGAVE ALHDHFYPDW MDF-NH2. Three smaller (less abundant) forms corresponded to the 30-, 21-, and 7-residue carboxyamidated C-terminal fragments. The major part was sulfated at the tyrosine residue in position seven from the C-terminus. A lower isoelectric point and abrupt termination of the sequencing suggest that some of the peptides had an isoAsp-Gly bond instead of an Asn-Gly bond. The three shorter forms were all derived from the precursor by post-Phe cleavages. This cleavage pattern suggests a processing enzyme specific for bonds between Phe and moderately hydrophobic residues.
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PMID:Identification of four chicken gastrins, obtained by processing at post-Phe bonds. 152 71

A rat islet amyloid polypeptide (amylin), 37-residue peptide amide was synthesized by the Fmoc-based solid phase method and the biological activity of synthetic rat amylin on exocrine pancreas was evaluated for the first time in conscious rat. Amylin (1, 10 nmol/kg/h) stimulated pancreatic exocrine secretion and plasma gastrin concentration. CR-1409, a CCK receptor antagonist, did not change amylin-stimulated pancreatic secretion. However, omeprazole (proton pump inhibitor) and atropine inhibited amylin-stimulated pancreatic secretion. This study suggests that amylin may play a role in biological action in the exocrine pancreas possibly mediated by gastric acid hypersecretion.
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PMID:Stimulatory effects of islet amyloid polypeptide (amylin) on exocrine pancreas and gastrin release in conscious rats. 157 8

In guinea pig isolated ileum longitudinal muscle myenteric plexus, cholecystokinin octapeptide (CCK-8S) produced a rapid (phasic) contraction followed by a slower tonic phase. The tetrapeptide derivative CCK-4 and pentagastrin elicited only the phasic response up to 10(-6) M, whereas the tonic phase was also apparent at higher concentrations. The rank order of potency for the effect of agonists on the tonic and phasic responses were CCK-8S much greater than gastrin greater than CCK-8US congruent to pentagastrin greater than CCK-4 and CCK-8S greater than gastrin congruent to pentagastrin greater than CCK-4 greater than CCK-8US, respectively. Phasic responses of CCK-8S and CCK-4 were sensitive to atropine, whereas the tonic response could be completely abolished with the neurokinin-1 antagonist GR82334. The CCK-A receptor antagonist L-364,718 up to 10(-7) M had little effect on the phasic contracture of CCK-4. The CCK-B/gastrin receptor antagonist L-365,260 had no effect on the CCK-8S phasic response up to 10(-7) M, but antagonized the phasic response induced by low concentrations of CCK-4 in a competitive manner with an estimated pKB of 8.51. This value is close to that of 8.53 found in a guinea pig cortical binding assay. Both the second phase of the CCK-4 phasic concentration response curve (CRC) and the tonic contraction were insensitive to L-365,260.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for two cholecystokinin receptors mediating the contraction of the guinea pig isolated ileum longitudinal muscle myenteric plexus. 160 72

We evaluated the affinity of cholecystokinin octapeptide (CCK-8), gastrin, and subtype-selective CCK agonists for CCK/gastrin receptors and compared it with the ability of these peptides to stimulate phosphoinositide (PI) hydrolysis and pepsinogen release in guinea pig gastric glands. Competitive binding studies using 125I-labeled Bolton-Hunter-CCK-8 and 125I-gastrin showed the presence of CCK-B/gastrin receptors in gastric glands and dispersed chief cells. In contrast, the potency of peptides in stimulating PI hydrolysis in both gastric glands and dispersed chief cells displayed a profile similar to CCK-A receptors found in pancreatic acini, i.e., CCK-8 = A 71378 greater than A 71623 greater than A 70874 much greater than A 72962 = CCK-8 (desulfated) greater than gastrin II greater than gastrin I. In general, the rank order of potency of peptides for stimulation of PI hydrolysis correlated well with their ability to stimulate pepsinogen release. At concentrations greater than 10 microM, efficacies of gastrin I and II in stimulating pepsinogen release from gastric glands were near 90% of the maximal activity of CCK-8. The inhibitory potency of MK-329, a selective CCK-A receptor antagonist, was similar against either CCK-8 (10 nM) or gastrin I (10 microM), except that a minor portion (approximately 30-40%) of gastrin I-induced pepsinogen release was insensitive to MK-329. The MK-329-insensitive component was inhibited by CI-988, a potent and selective CCK-B/gastrin receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Both CCK-A and CCK-B/gastrin receptors mediate pepsinogen release in guinea pig gastric glands. 161 41

The control of cell proliferation by gastrin has been investigated in a rat pancreatic tumour cell line, AR4-2J. Exogenous gastrin, 10(-12) to 10(-8) M, stimulated cell growth of thymidine-synchronised AR4-2J cells cultured over 48 h in serum-free medium. Cell lysates of AR4-2J cells contained an average of 4.5 and 3.5 pg gastrin per 10(6) cells, when grown in serum-supplemented or serum-free media, respectively, as revealed by radioimmunoassay. In serum-free medium, AR4-2J secrete 34 ng 1(-1) 10(-6) cells of gastrin over 48 h. Addition of an anti-gastrin immunoglobulin preparation, but not control immunoglobulins, caused a maximum 52% reduction in cell growth. These data are consistent with an autocrine role for gastrin in the control of AR4-2J cell growth. These results were supported by studies with gastrin/CCK receptor antagonists. Six non-peptide gastrin/CCK receptor antagonists inhibited AR4-2J cell growth in a concentration-related manner. The concentration required for 50% inhibition (IC50) of cell growth by the amino acid-derived antagonists proglumide (3.5 x 10(-3) M), benzotript (1.8 x 10(-3) M), loxiglumide (1.1 x 10(-4) M) and lorglumide (6.7 x 10(-5) M) were of the same order and significantly correlated with their IC50 for inhibition of 125I-gastrin binding to AR4-2J cells. Inhibition of cell growth by these antagonists was partially reversed by the addition of exogenous gastrin. In contrast, the IC50 for inhibition of cell growth with two benzodiazepine-derived antagonists, the CCK-B receptor antagonist L-365,260 (4.6 x 10(-5) M) and the CCK-A receptor antagonist devazepide (1.7 x 10(-5) M) were two-three orders of magnitude greater than those required to inhibit gastrin binding (10(-8)-10(-7) M). The growth inhibitory effects of L-365,260 and devazepide were not reversed by exogenous gastrin suggesting these benzodiazepine-derived antagonists do not inhibit cell growth by interaction with gastrin receptors. The results are consistent with gastrin being an autocrine growth factor in AR4-2J cells, and that stimulation of cell growth is due to stimulation of the gastrin, rather than CCK-B, receptor sub-type. This study highlights that gastrin receptor antagonists warrant further investigation as agents to control growth of tumours, such as those from the gastrointestinal tract, which express gastrin receptors.
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PMID:Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin. 163 73

Gastrin has significant growth and metabolic effects on colonic mucosal cells. It is, however, not known if gastrin receptors are present on colonic mucosal cells that may directly mediate the reported biological effects of gastrin. In the present studies, the presence of specific gastrin binding sites on colonic mucosal membranes was investigated and the binding sites were further characterized. Crude membranes from colonic mucosa of guinea pigs were analyzed for specific binding to gastrin by our published procedures. A significant number (14.7 +/- 1.8 fmoles/mg protein) of high affinity gastrin binding sites (Kd = 0.49 +/- 0.05 mM) were measured, that were specific for binding gastrin/CCK related peptides and demonstrated negligible binding affinity for all other unrelated peptides examined. In addition a large number of low-affinity (Kd = approximately 1 microM) binding sites were present. In order to further characterize the molecular size of gastrin binding proteins, we used the chemical cross-linking methods, and observed at least four bands of gastrin binding proteins (GBPs) (approximately 33, 45, 80 and 250 KDa), both under reducing and non-reducing conditions, indicating that these proteins were not sub-units of forms linked by disulfide bonds. Interestingly, majority of the specific gastrin binding sites (approximately 70%) were present on the 45 KDa protein, unlike other target cells of gastrin. The presence of N- and O-linked glycosylated moieties were indicated on the 45 KDa protein, based on enzymatic de-glycosylation studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of gastrin binding to colonic mucosal membranes of guinea pigs. 164 Sep 30

To evaluate whether pretreatment with prostaglandin E2 (PGE2) could desensitize pepsinogen secretion in chief cells from guinea pig, chief cells were pretreated with 10 microM PGE2 for up to 30 min. Desensitization of subsequent PGE2-stimulated secretion was maximal after 15 min, averaging only 29 +/- 9% (SE) of pepsinogen secretion in control cells stimulated with 10 microM PGE2. Desensitization was half-maximal with 30 nM PGE2. PGE2 pretreatment at 4 degrees C did not cause desensitization. In cells pretreated with 10 microM PGE2 for 15 min and then given 60 min to recover, responsiveness increased to 79 +/- 7% of that for control cells stimulated with PGE2. Thus the desensitization was reversible. Pretreatment with PGD2 and PGF2a did not alter subsequent PGE2-mediated secretion. PGE2-induced desensitization was heterologous but mediator specific because pepsinogen secretion was reduced in response to adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (secretin and vasoactive intestinal peptide) but not Ca(2+)-mediated agents (CCK-8, gastrin, or carbachol). Pretreating chief cells with 10 microM PGE2 did not significantly alter cAMP generation in response to PGE2, secretin, or 3-isobutyl-1-methylxanthine, suggesting that desensitization was not mediated by an alteration in the receptor-coupled adenylate cyclase system. Because PGE2 pretreatment also desensitized pepsinogen secretion induced by the synthetic cAMP analogues 8-BrcAMP and 2'-O-monobutyryl-8-BrcAMP, it is likely that the ability of PGE2 to desensitize pepsinogen secretion in chief cells isolated from guinea pig is due to a mechanism distal to generation of cAMP.
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PMID:Prostaglandin E2 desensitizes cAMP-mediated pepsinogen secretion in chief cells. 165 22

The isolated gastric gland preparation, with aminopyrine accumulation as an index of the parietal cell response, has been used to study the effects of somatostatin (S-14), gastrin-releasing peptide (GRP), cholecystokinin (CCK-8), vasoactive intestinal peptide (VIP), and peptide YY (PYY) on the in vitro acid secretion in human and rabbit oxyntic mucosa. Somatostatin was able to inhibit the parietal cell response to histamine in both human and rabbit isolated gastric glands (maximal inhibition, 22% and 34%, respectively) but failed to inhibit the parietal cell response to db-cAMP. However, other peptides capable of inhibiting gastric acid secretion in vivo, such as CCK, VIP, and PYY, were unable to induce any inhibition of the parietal cell response to db-cAMP or histamine in the isolated gastric gland preparation irrespective of the species studied. GRP was not able to induce a parietal cell response, a finding that is in accord with the assumption that the stimulatory effect of GRP on gastric acid secretion in vivo is by releasing gastrin from antral G-cells.
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PMID:Effects of some gastrointestinal peptides on isolated human and rabbit gastric glands. 167 70

Cholecystokinin octapeptide (CCK-8), ceruletide (CLT) and gastrin-I, which were added simultaneously with glutamate to rat neuron cultures, significantly suppressed the neuronal cell death induced by glutamate which can be observed from the efflux of lactate dehydroxylase into the culture medium. However, gastrin-I (1-13) had no effect on the response to glutamate. The inhibitory effect of CLT on glutamate-induced neuronal cell death could be completely blocked by a selective antagonist for CCK-B receptors, (+)L-365,260. These findings clearly indicate that CCK-8, CLT and gastrin-I exhibit a protective effect against glutamate-induced neurotoxicity via the CCK-B receptor.
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PMID:Protective effect of CCK-8 and ceruletide on glutamate-induced neuronal cell death in rat neuron cultures: possible involvement of CCK-B receptors. 168 72

The effects of bombesin on the growth of the gastroduodenal mucosa and the pancreas have been examined in adult rats with intact or resected antrum and following administration of somatostatin or CCK-receptor antagonist L-364,718. The peptides were administered three times daily for 7 consecutive days, and then the animals were sacrificed and growth parameters (organ weight and RNA and DNA contents) were determined, and plasma gastrin and CCK were assayed. Compared with the control (saline) values, bombesin significantly stimulated the growth of the oxyntic and duodenal mucosa and the pancreas. These effects were partly reduced but not abolished by somatostatin, antrectomy and L-364,718, suggesting that bombesin may enhance the growth partly by releasing gastrin and CCK and partly by direct action on these tissues.
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PMID:Role of gastrin and cholecystokinin in the growth-promoting action of bombesin on the gastroduodenal mucosa and the pancreas. 169 18


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