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)

A method is described for the isolation and short-term culture of canine antral gastrin (G) cells. Tissue was dispersed by enzymes and G cells enriched by elutriation and cultured for 40 h. These cultures contained 12% G cells and less than 2% somatostatin- or serotonin-containing cells. Bombesin (0.001-100 pM) potently stimulated gastrin release from cell cultures in a linear fashion over 2 h. The bombesin-specific monoclonal antibody 2A11 dose-dependently blocked bombesin stimulation. Somatostatin (0.001-1,000 nM) inhibited bombesin-stimulated gastrin release. Antibody to somatostatin (Mab S8) prevented the inhibition by exogenous somatostatin but did not alter bombesin-stimulated or basal gastrin release. The substance P (SP) analogue spantide (1 nM-1 microM) did not inhibit bombesin-stimulated gastrin release. Postreceptor activation of adenylate cyclase by forskolin and of protein kinase C by the phorbol ester, beta-TPA, caused gastrin release. The calcium ionophore A23187 also released gastrin in a dose-dependent fashion. This methodology allows enrichment and short-term culture of antral G cells; these cells have stimulatory bombesin and inhibitory somatostatin receptors, suggesting that these peptides have a direct action on antral G cells. Furthermore, G cells are activated by cAMP and calcium/phosphatidylinositol-dependent mechanisms.
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PMID:Bombesin stimulation of gastrin release from canine gastrin cells in primary culture. 243 71

The effect of a new proglumide derivative, loxiglumide (DL-4-(3,4-dichloro-benzoyl-amino)-5-(N-3-methoxy-propyl-pentylamino+ ++)-5-oxo-pentanic acid; CR 1505), on binding of 125I-CCK-8 and amylase release stimulated by CCK-8 was investigated in isolated rat pancreatic acini. Loxiglumide inhibited CCK-8-stimulated amylase release and binding of 125I-CCK-8 to rat pancreatic acini in a dose-dependent manner. Loxiglumide caused a concentration-dependent rightward shift of the dose-response curve for CCK-8-stimulated amylase release without altering the maximal response. Schild plots showed a slope of 0.82 and pA2 value of 7.05. The inhibitory effect of loxiglumide on amylase release was reversible. Loxiglumide significantly inhibited amylase release in response to CCK-8, caerulein and gastrin-I. However, loxiglumide had no effect on amylase release stimulated by other receptor secretagogues (bombesin, carbamylcholine, secretion and vasoactive intestinal polypeptide) or by agents bypassing receptors (A23187 and TPA). These results indicate that loxiglumide acts as a potent, competitive and specific CCK antagonist on the pancreatic acini.
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PMID:[Inhibitory effect of a new proglumide derivative, loxiglumide, on CCK action in isolated rat pancreatic acini]. 247 51

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.
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PMID:Control of gastrin release in cultured gastrinoma-derived G cells. 289 16

Neuropeptides such as gastrin releasing peptide and pituitary adenylate cyclase activating polypeptide (PACAP) stimulate CCK secretion from CCK producing cells. We hypothesized that in addition to somatostatin, galanin may also play an inhibitory role on CCK secretion. The effect of galanin on CCK secretion was studied in a CCK-producing murine neuroendocrine tumor cell line, STC-1. Galanin below 10 nM did not affect basal CCK secretion but dose- and time-dependently inhibited KCl-stimulated CCK secretion. Galanin also inhibited forskolin-, bombesin- and PACAP- but not dibutyryl cAMP- or beta-TPA-stimulated CCK secretion. The inhibitory effect of galanin was reduced partially by a blocker of ATP-sensitive K+ channel (K+ ATP), glibenclamide, and prevented by pretreatment of the cells with PTX. The results indicated galanin regulates CCK secretion by modulation of K+ ATP and cAMP production through receptors coupled to a PTX-sensitive G protein.
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PMID:Galanin inhibits cholecystokinin secretion in STC-1 cells. 748 89

Gastrin and cholecystokinin (CCK) have proven trophic effects on the gut. We have previously demonstrated that these peptides stimulate an early event in cellular proliferation, namely ornithine decarboxylase activity (ODC), in a rat exocrine pancreatic cell line AR4-2J. Furthermore, this effect is mediated through a G/CCKB receptor. Thus, in the present study we sought to examine the signal transduction mechanisms linked to the G/CCKB receptor occupancy. Both gastrin and CCK induced a rapid (maximum at 40 s) increase in inositol triphosphates (InsP3) and diacylglycerol (DAG) formation in a dose-dependent manner (EC50 = 5.6 nM) that quickly returned to baseline. Although InsP3 levels remained at baseline, DAG levels demonstrated a second gradual increase that was maximal at 15 min. CCK/gastrin efficiency to stimulate DAG and InsP3 formation (EC50 = 5.6 nM) could be correlated to the G/CCKB receptor occupancy, suggesting a coupling of this receptor to phospholipase C. To examine the involvement of protein kinase C (PKC) activation in the increase in ODC activity, we stimulated the AR4-2J cells with the phorbol ester TPA and observed an increase in ODC activity with a maximal effect at 100 nM. TPA stimulation of ODC activity was completely abolished by the PKC inhibitor staurosporine (50 nM). However, 50 nM staurosporine inhibited only 65% of the gastrin and CCK induced increase in ODC activity suggesting that a portion of the G/CCKB receptor-mediated increase in ODC activity is PKC independent.
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PMID:Coupling of pancreatic gastrin/cholecystokinin-B (G/CCKB) receptors to phospholipase C and protein kinase C in AR4-2J tumoral cells. 797 29

The effects of cyclic adenosine monophosphate-dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) modulators on secretagogue-stimulated gastric acid secretion were studied in the continuously perfused stomach of the anesthetized rat. Intravenous histamine (0.25 mg/kg/h) and pentagastrin (2 micrograms/kg/h) increased secretion above baseline by three- and fourfold, respectively. Parenteral administration of a PKC activator, 12-o-tetradecanoylphorbol-13-acetate (TPA; 0.1 nmol/h), decreased histamine- and pentagastrin-stimulated secretion by 64 and 40%, respectively. Administration of PKC inhibitors, calphostin C and 1-(5-isoquinolinyl sulfonyl)-2 methylpiperazine (H-7; 10 nmol/h, each), increased histamine- and pentagastrin-stimulated secretion by 115 and 74% and 42 and 79%, respectively, while equimolar concentrations (10 nmol/h) of three other isoquinoline sulfonamides (HA-1004, H-8, and H-89) had no effect, except for H-89 (100 nmol/h) which inhibited the histamine- and penta-gastrin-stimulated acid secretion by 44%. Basal secretion was not significantly altered by the aforementioned drugs. The TPA-induced inhibition of pentagastrin-stimulated secretion was partially reversed by treatment with H-7. These findings support a role of PKA and PKC in the modulation of stimulated gastric acid secretion in vivo.
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PMID:Effects of cyclic adenosine monophosphate-dependent protein kinase and calcium-dependent protein kinase modulators on stimulated gastric acid secretion in the perfused rat stomach. 857 20