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)

Clinical data indicate that the control of gastrin secretion from the human antrum has a beta-adrenergic component. The purpose of the present study was to investigate whether this was due to the presence of beta-adrenergic receptors on the G cells. A newly developed short-term culture system of enriched antral G cells was used to eliminate the possibility of input from factors in the circulation and the peripheral innervation. The results demonstrated that epinephrine and terbutaline (a beta 2 agonist) significantly stimulated gastrin release above basal which could be blocked by the addition of propranolol (beta-adrenergic antagonist). However, the beta 1 agonist, dobutamine, and phenylepinephrine did not stimulate gastrin release above basal. In addition, simultaneous administration of epinephrine and the neuropeptide, bombesin, resulted in a potentiation of gastrin release. It was concluded that the stimulatory effect of the sympathetic system on gastrin release was mediated through beta 2-adrenergic receptors. The data indicated that adrenaline released from the adrenal medulla and gastrin releasing peptide (the mammalian homolog of bombesin) released from the intrinsic innervation of the stomach interact with respect to the stimulation of gastrin.
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PMID:Effect of sympathomimetics on gastrin secretion from antral G cells in culture. 167 96

Experimental studies located carbonic anhydrase (CA) in the parietal cells close to secretory canaliculi, in superficial epithelial cells and gastric microvasculature. The role of CA is CO2 hydration resulting H+ for acid secretion and conversion of OH into HCO3-. Our studies showed that the physiological secretagogue histamine, acetylcholine and gastrin are all CA activators, achieving potentiating interactions. Catecholamines are also strong enzymatic activators. Beside sulfonamides, other CA inhibitors are anticholinergics, PGE and PGI2, some calcium channel blockers, alpha 2- and beta 1-adrenoceptor blockers and Zn2+. Cytoprotective properties of CA inhibitors gained experimental evidence in the past years. These effects could be based on increase of gastric mucosal blood flow, proved experimentally, which might be mediated by increase of endogenous prostaglandin synthesis and sulfhydryls and, respectively, motility changes. The unique combination of strong antisecretory effect with the cytoprotective action explain the outstanding clinical efficacy of CA inhibitors in the healing of gastric and duodenal ulcers.
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PMID:Carbonic anhydrase inhibitors: antisecretory and cytoprotective properties. 251 64

The effect of adrenergic agonists and antagonists on the secretion of gastric somatostatin-like immunoreactivity (SLI) and gastrin was investigated in an isolated, vascularly perfused rat stomach preparation. Two- to six-fold increases in SLI secretion induced by isoproterenol, epinephrine, and norepinephrine were completely abolished by propranolol but were not influenced by phentolamine. Propranolol did not alter glucagon- and DB-cAMP-induced stimulation of SLI release. Experiments in which the beta 2-agonist salbutamol and the beta 1- and beta 2-blockers practolol and H35/25 were used showed that both subtypes of beta receptors are involved. Gastrin secretion revealed only minor changes in dose-response studies with a wide range of isoproterenol concentrations (2 X 10(-8) to 1.5 X 10(-4) M). The results obtained in this study suggest that in rats 1) the SLI response to adrenergic agonism is predominantly mediated by beta receptors; 2) both beta 1- and beta 2-adrenergic receptors are involved; 3) under in vitro conditions, adrenergic agonism is a weak stimulus for gastrin secretion.
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PMID:Adrenergic control of rat gastric somatostatin and gastrin release. 614 72

The actions of adrenoceptor agonists and antagonists are by no means agreed even though experiments with adrenal medulla extract date back to the beginning of the century. This review will consider the work of my own group and that of others in an attempt to classify the adrenoceptors which modulate gastric acid secretion. There are a number of factors to consider. Species differences are important and particular attention will be given to results from rat, dog and human. The secretagogue used is also important because the effect of adrenoceptor agonists and antagonists can be modified by the choice of histamine, muscarinic agonist, (penta) gastrin or food. Other factors include the gastric model used and the presence or absence of anaesthesia. The broad conclusions are that both alpha- and beta-adrenoceptors can inhibit gastric acid secretion. Both beta 1- and beta 2-adrenoceptors mediate inhibition of pentagastrin-induced secretion while alpha-adrenoceptors are important in the reduction of histamine-induced gastric acid secretion.
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PMID:The classification of adrenoceptors and their effects on gastric acid secretion. 614 92

The beta 3-adrenoceptor (beta 3-AR) agonist SR-58611A {ethyl-[(7s)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]5, 6,7,8-tetrahydronaphth-2-yl]oxyacetate hydrochloride} stimulated somatostatin and gastrin releases in isolated rat gastric antral epithelial cells. Stimulation was a concentration-dependent process with 50% effective concentrations of 2.7 +/- 1.1 and 3.8 +/- 1.9 nM compared with 209 +/- 71 and 230 +/- 51 nM for isoproterenol, respectively. It was inhibited by selective beta-AR antagonists with the following rank order of potency: SR-59230A 3-(2-ethylphenoxy)1-[(1S)-1,2,3,4-tetrahydronaphth- 1-ylamino]-(2S)-2-propranol oxalate; beta 3-AR antagonist > ICI-118551[erythro-(+/-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride; beta 2-AR antagonist > CGP-20712A[(+/-)-[2-(3-carbarmoyl-4-hydroxyphenoxy)-et hyl- amino]-3-[4 (1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]- 2-propranol; beta 1-AR antagonist]. Furthermore, specific binding of 125I-cyanopindolol to the isolated cells was demonstrated and was displaced by the beta-AR antagonists according to the same rank order of potency and with apparent dissociation constants consistent with the 50% inhibitory concentrations for SR-58611A-stimulated somatostatin and gastrin releases. In addition, the presence of beta 3-AR mRNA was detected by reverse transcriptase polymerase chain reaction. These findings provide the first evidence for a gastric beta 3-AR mediating catecholamine stimulation of gastrin and somatostatin releases from antral cells.
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PMID:Characterization of a beta 3-adrenoceptor stimulating gastrin and somatostatin secretions in rat antrum. 917 7

We have previously reported that gastrin induces a rapid and transient tyrosine phosphorylation of phospholipase C gamma 1 (PLC gamma 1) in association with inositol 1,4,5-trisphosphate (IP3) formation in rat colonic epithelial cells (34). In this study, we demonstrate that gastrin regulates IP3 formation mainly through PLC gamma 1 isozyme. Immunoblotting analysis revealed the expression of PLC beta 3 and -gamma 1, but not PLC beta 1, -beta 2, or -beta 4 in the rat colonic epitheliums. To explore what PLC isozyme(s) modulates gastrin effect on IP3, immunoneutralizing antibody to PLC beta 1, -beta 3, or -gamma 1 was introduced into the colonic cells using a lipid carrier. The gastrin-stimulated increase in IP3 concentration was specifically prevented by anti-PLC gamma 1 but not by anti-PLC beta 1 or -beta 3 antibody. Immunoprecipitation assays have also revealed that gastrin promoted an increase in tyrosine phosphorylation and co-precipitation of a 60 kDa src kinase with PLC gamma 1. Administration of antibody specific to pp60c-src into the colonic cells prevented the gastrin-stimulated increases in IP3. Tyrosine phosphorylation of PLC gamma 1 may be a major mechanism through which gastrin regulates IP3 level in the colonic cells. Pretreatment of cells with the tyrosine kinase inhibitor genistein abrogated gastrin's effect on IP3, while extended pretreatment with pertussis toxin, a G-protein inhibitor, did not affect the ability of gastrin to stimulate IP3 formation. Colonic cells expressed the G alpha i subunits1-3; however, immunoblotting analysis did not reveal any difference in G alpha i proteins' expression between control and gastrin treated cells. The results provide direct evidence that gastrin regulates IP3 level by a signaling mechanism that involves PLC gamma 1 and pp60c-src kinase.
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PMID:Gastrin induces IP3 formation through phospholipase C gamma 1 and pp60c-src kinase. 943 36

Pancreatic endocrine neoplasms are neoplastic proliferations of islet cells or islet cell precursors and are capable of secreting a variety of synthetic products, including insulin, glucagon, gastrin, and vasoactive intestinal peptide. The biological behavior of pancreatic endocrine neoplasms is often unpredictable, and there are few reliable histopathologic criteria reliably correlating with metastatic ability. We have used the Affymetrix U133 GeneChip set (HG_U133 A and B; Affymetrix; Santa Clara, CA) representing approximately 33,000 characterized transcripts to examine global gene expression profiles from well-differentiated nonmetastatic (n=5) and metastatic (n=7) pancreatic endocrine neoplasms to determine molecular markers that predict disease progression. Microarray hybridization data were normalized using the GeneLogic GeneExpress Software System to identify differentially up- and down-regulated genes in metastatic versus nonmetastatic pancreatic endocrine neoplasms. Using a 3-fold change in gene expression as a threshold, we have identified 65 overexpressed and 57 underexpressed genes in metastatic pancreatic endocrine neoplasms as compared with nonmetastatic pancreatic endocrine neoplasms. Several classes of genes, including growth factors and growth factor-related molecules (IGFBP1, IGFBP3, and MET), developmental factors (TBX3 and MEIS2), cytoskeletal factors (beta 1 tubulin and ACTN2), cholesterol homeostasis mediators (LRP5, SLC27A2, and RXRG), intracellular signaling pathway mediators (DYRK1A, PKIB, and AK2), methyltransferases (MGMT and GAMT), and DNA repair and regulatory molecules (CHEK1 and ZNF198), were identified as differentially over- or underexpressed via this method. Immunohistochemical validation of microarray data were performed for two overexpressed genes, namely, the met proto-oncogene (MET) and insulin-like growth factor binding protein 3 (IGFBP3) with tissue microarrays of nonmetastatic (n=24) and metastatic (n=15) pancreatic endocrine neoplasms. Increased expression of IGFBP3 was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (12 of 15, 80% versus 10 of 24, 42%), as well as in lymph node (6 of 7, 86%) and liver (9 of 9, 100%) metastases. Similarly, overexpression of MET was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (5 of 15, 33% versus 4 of 24, 17%), as well as in lymph node metastases (4 of 7, 57%) and liver metastases (5 of 9, 56%). The majority of genes that demonstrated altered expression has not been previously identified as differentially expressed in metastatic pancreatic endocrine neoplasm lesions and may therefore represent newly identified molecules in the progression of these lesions.
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PMID:Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. 1544 2