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)

Previous studies have demonstrated that gastrin and the COOH-terminal octapeptide of cholecystokinin (CCK-8) stimulated in vitro acid secretion from isolated rabbit gastric parietal cells. Both peptides bind to receptor sites located on these cells and induce an increase in phosphoinositide turnover and an uptake of [14C]aminopyrine ([14C]AP) with the same efficacy and potency. In the present study, we used the 3-(benzoylamino)-benzodiazepine analogue L365,260 and the 3-(acylamino)-benzodiazepine analogue L364,718 to investigate what type of receptor (gastrin type or CCK-A type) is involved in the regulation of the H+ secretory activity of the rabbit parietal cell. Neither L365,260 nor L364,718 alone caused stimulation of [3H]inositol phosphates ([3H]InsP) production. Each analogue inhibited 125I-labeled gastrin or 125I-CCK-8 binding to parietal cells and gastrin- or CCK-8-induced [3H]InsP production and [14C]AP accumulation. In all cases, L365,260 was approximately 70-100 times more potent than L364,718 (IC50 approximately 2-4 nM for L365,260 and approximately 0.2-0.4 microM for L364,718). Nevertheless, each antagonist displayed the same potency to inhibit the effects of gastrin or CCK-8. These results demonstrate that gastrin and CCK-8 interact with the same "gastrin-type" receptor on parietal cells. Moreover, L365,260 behaves as a competitive antagonist of the action of gastrin on parietal cells. Gastrin induces a rise in the levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] within the first seconds after parietal cell stimulation. The fact that L365,260 (10 nM) totally suppressed the gastrin-induced formation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 suggests the involvement of these isomers in the mediation of acid secretion through gastrin receptor activation.
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PMID:Characterization of a gastrin-type receptor on rabbit gastric parietal cells using L365,260 and L364,718. 199 38

The role of phosphoinositide turnover in the mediation of acid secretion was examined in an enriched preparation of isolated rabbit parietal cells (75%). Both gastrin and CCK-8 (octapeptide of cholecystokinin) stimulated [14C]aminopyrine (AP) uptake by cells (EC50 0.07 +/- 0.03 nM (gastrin) and 0.093 +/- 0.065 nM (CCK-8] and increased [3H]inositol phosphates cellular contents (EC50 0.142 +/- 0.016 nM (gastrin) and 0.116 +/- 0.027 nM (CCK-8] in a parallel fashion. In addition, the EC50 values for both phenomenon were quite similar to the Kd values obtained from binding experiments. HPLC analysis of the different [3H]inositol phosphates produced under gastrin or CCK-8 stimulation showed a 2-fold increase in [3H]Ins(1,4,5)P3 levels within 5 s with a concomitant increase in [3H]Ins(1,4)P2 content within 15 s. A low but significant rise in [3H]Ins(1,3,4,5)P4 and [3H]Ins(1,3,4)P3 cellular contents was also observed. No difference between gastrin- and CCK-8-induced inositol phosphates production could be shown. We can conclude that gastrin and CCK-8 display an identical profile of action, suggesting that they stimulate the acid secretory function of parietal cells through the same receptor site coupled to the Ins(1,4,5)P3 production.
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PMID:Gastrin and CCK-8 induce inositol 1,4,5-trisphosphate formation in rabbit gastric parietal cells. 255 25

The goal of this study was to engineer gastrin-producing G cells of the gastric antrum to produce insulin. A pGas-Ins chimeric gene in which the gastrin promoter drives expression of the human insulin gene was constructed and was validated by transient transfection of GH4 and AGS cells. RT-PCR analysis and sequencing revealed three forms of differentially spliced insulin mRNA in GH4 cells transiently transfected by pGas-Ins. Gas-Ins transgenic mice were generated utilizing this chimeric gene. Northern blot analysis, in situ hybridization, and immunohistochemistry demonstrated expression of the human insulin gene specifically in antral G cells. Northern blot analysis demonstrated that the shortest of the insulin mRNA three forms is predominantly expressed in stomach tissue. RT-PCR analysis also showed expression of the transgene in colon, pancreas, and brain tissues that was undetectable by northern analysis. We conclude that gastrin promoter can be used for targeting expression of human insulin to antral G cells and that antral G cells can express human insulin. Further refining of the chimeric gene design is required to enhance expression.
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PMID:Expression of the human insulin gene in the gastric G cells of transgenic mice. 1159 12