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

The mechanism by which the gastrointestinal hormones peptide YY and glucagon inhibit gastric acid secretion is largely unknown. PYY-Tag transgenic mice develop endocrine tumors in the colon that are composed mainly of peptide YY/enteroglucagon-producing L type cells. Therefore we studied the functional activity of such tumors and the gastric functions of PYY-Tag mice. Fasting and fed PYY-Tag transgenic mice and CD1 controls were assayed for circulating levels of peptide YY, glucagon, insulin, and gastrin. The gastric pH was determined and gastric samples were examined for (a) histologic appearance; (b) K(+)-stimulated p-nitrophenylphosphatase activity and [(14)C]aminopyrine accumulation of apical and tubulovesicle membranes; (c) adherent mucus determination by Alcian blue recovery; and (d) DNA/RNA/protein epithelial content and in vivo incorporation of [(3)H]thymidine into DNA. Transgenic mice showed high serum levels of peptide YY and glucagon, increased gastric pH, and a high incidence of gastric ulcers after fasting. p-Nitrophenylphosphatase activity, [(14)C] aminopyrine accumulation, and proton pump redistribution from cytoplasmic tubulovesicles to apical membranes were significantly lower in the gastric mucosa of transgenic mice compared with the controls. In addition, the adherent mucus was thinner, and [(3)H]thymidine incorporation into the DNA was decreased. The abnormal and unregulated levels of circulating peptide YY and glucagon led to gastric acid inhibition and an impairment of gastric barrier function as a result of a striking reduction in epithelial proliferation.
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PMID:PYY-Tag transgenic mice displaying abnormal (H+-K+)ATPase activity and gastric mucosal barrier impairment. 1253 85

Endogenous cholecystokinin tetrapeptide (CCK-4, Trp-Met-Asp-Phe-NH2) is a fragment derived from a larger peptide hormone, cholecystokinin (or gastrin). As a panicogenic agent, CCK-4 is commonly used in clinic settings to induce panic attacks for the study of new anxiolytic drugs. However, few studies on CCK-4 metabolism have been published to date. In the present study, we investigate the metabolism of CCK-4 in liver microsomes of human (HLM), Rhesus Monkey (RMLM), Sprague-Dawley rat (RLM) and CD1 mouse (MLM) using ultra-high performance liquid chromatography coupled to a high resolution mass spetrometer. Ten metabolites, inlcuding tryptophan (M1), tryptophan amide (M2), hydroxy metabolites (M3-M5), truncated peptides (M6-M9), and CCK-4 acid (M10), were identified and 8 of them were reported for the first time. The metabolic pattern of CCK-4 in HLM was distinctly different from these in RMLM, RLM, and MLM. M2 and M9 were the major metabolites in HLM and accounted for 19.8% and 13.4% of initial CCK-4, respectively. In contrast, M2 was the major metabolite in RMLM and accounted for 41.4%, whereas M6 was the major metabolite in RLM and account for 39.1%. Three major metabolites M2, M7 and M8 in MLM accounted for 22.6%, 17.9% and 17.8% of initial CCK-4, respectively. Chemical inhibition experiment showed that aminopeptidase and/or endopeptidase hydrolysis were the major metabolic pathways in human to generate these metabolites. We further showed that cytochrome P450 were also involved in the metabolism of CCK-4 via hydroxylation, but to a less extend. These findings provide valuable information for the metabolic processes of CCK-4 among various species and an important reference basis for its safety evaluation and rational clinical application.
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PMID:Identification of cholecystokinin tetrapeptide amide metabolites in liver microsomes of human, Rhesus Monkey, Sprague-Dawley rat and CD1 mouse using ultra-high performance liquid chromatography coupled to high resolution mass spectrometer. 3014 98