Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the truncated 7-37 glucagon-like peptide 1 (TGLP-1), a naturally occurring porcine intestinal peptide, and other members of the glucagon family, including pancreatic glucagon (G-29), GLP-1 and GLP-2 for their ability to activate the cAMP generating system in rat gastric glands and HGT-1 human gastric cancer cells. In rat fundic glands, TGLP-1 was about 100 times more potent (EC50 = 2.8 X 10(-9) M) than GLP-1 of G-29, and 10 times more potent than G-29 in the HGT-1 cell line. Our results support the notion that TGLP-1 plays a direct role in the regulation of acid secretion in rat and human gastric mucosa.
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PMID:Effect of truncated glucagon-like peptide 1 on cAMP in rat gastric glands and HGT-1 human gastric cancer cells. 284 Nov 60

Homologous loss of histamine H2-receptor activity (cAMP generation) was observed after short-term (10-20 min) or chronic treatment (6 days) of cultured HGT-1 cells with histamine (desensitization) or the H2-receptor antagonist SKF 93479. This inactivation process was not observed when HGT-1 cells were exposed to the classical H2-antihistamine cimetidine. The data show: (1) that the compound SKF 93479 has a very prolonged inhibitory action on histamine receptor activity, suggesting an irreversible interaction between the antagonist and the receptor; (2) that cimetidine is a reversible H2-receptor antagonist which can be removed without changing the the efficacy and the potency of histamine on gastric cells; (3) that the H2-receptor antagonists cimetidine and SKF 93479 specifically block histamine H2-receptor activity in HGT-1 cells since cAMP generation induced by other hormones such as vasoactive intestinal peptide (VIP), glucagon or gastric inhibitory peptide (GIP) was unchanged after treatment; (4) the first evidence for time-dependent (half-life: 20 min) desensitization of gastric H2-receptors.
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PMID:Selective disappearance of histamine H2-receptor activity in the human gastric cancer cell line HGT-1 after short-term or chronic treatment by histamine or its H2-antagonists. 286 31

Imidazole and isocytosine-furan derivatives inhibited H2 receptor activity in HGT-1 cells, in accordance with the following relative potencies (IC50 = 2.3 microM cimetidine as reference): SKF 93479 = cimetidine = 100 greater than metiamide = 62 greater than SKF 92408 = 2 greater than SKF 91581 = 0.07). The Schild plot for cimetidine was linear (slope = 0.97) with a pA2 value of 6.72 +/- 0.12 (Ki = 0.18 microM cimetidine), suggesting competitive inhibition. Preincubation of HGT-1 cells for 10 min with H2 antagonists at 2 microM concentration resulted in 90-100% inactivation (SKF 93479 and oxmetidine) and 65% inactivation (ranitidine) which persisted for 30 min, even after a washout period. Accordingly, the kinetics of 2 microM [3H] SKF 93479 binding to HGT-1 cells revealed a half-time for association of 10 min and a dissociation half-time of 120 min. There was a good correlation between the kinetics and relative potencies of cimetidine and SKF 93479 in inhibiting H2 receptor activity in purified plasma membranes (40 nM) as well as in intact HGT-1 cells preincubated for 2 hr with SKF 93479 before histamine addition (45 nM). Chronic treatment of HGT-1 cells for 6 days with 2 microM SKF 93479 specifically blocked H2 receptor activity since cyclic AMP generation induced by other hormones and agents such as VIP, glucagon, GIP and sodium fluoride was unaltered. In contrast, short term and chronic treatment by cimetidine was readily reversible. The isocytosine-furan derivative SKF 93479 differs from the imidazole analogue cimetidine by its apparent irreversible action, due to the slow onset of association from HGT-1 cells. The isocytosine ring in SKF 93479 and oxmetidine seems to play a preponderant role in their apparent long-lasting, irreversible actions.
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PMID:Pharmacology of histamine H2 receptor antagonists in the human gastric cancer cell line HGT-1. Structure-activity relationship of isocytosine-furan and imidazole derivatives related to cimetidine. 287 95

Three separate sets of receptors sensitive to VIP, GIP and pancreatic/entero-glucagons, have been characterized in HGT-1 cells. The order of relative potencies of VIP receptor agonists was VIP greater than rh GRF-43, rh GRF-29 greater than PHI greater than hp GRF-40, secretin. G-37 was about 4 times less potent than G-29 in HGT-1 cells (G-29 greater than G-37), whereas it was about 20 times more potent than G-29 in rat fundic glands (G-37 greater than G-29). Adenylate cyclase in HGT-1 cells was stimulated by VIP, G-29, G-37 and GIP, over a concentration from 3.16 X 10(-9) to 3.16 X 10(-7) M GIP. The experimental data: (1) support the enterogastrone activity of GIP, via adenylate cyclase activation and somatostatin release by gastric D cells; (2) demonstrate that HGT-1 cells originating from a human fundic tumor are sensitive to the glucagon-like peptides G-29 and -37, as rat fundic glands; (3) indicate that the pharmacological properties of the VIP receptor in this human gastric cell line are similar to those characterized in normal human gastric glands.
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PMID:Functional receptors for VIP, GIP, glucagon-29 and -37 in the HGT-1 human gastric cancer cell line. 301 90

GIP (EC50 = 8 X 10(-9) M, 5-fold stimulation), pancreatic glucagon (EC50 = 10(-8)M, 13-fold) and porcine or chicken VIP (EC50 = 2.5 X 10(-9) M, 10-fold) are shown to activate the cAMP generating system in HGT -1 cells. Combinations of GIP, pancreatic glucagon and VIP indicate the occurrence of 3 separate sets of recognitions sites for these 3 peptides. Accordingly, chronic treatment of cultured HGT -1 cells by VIP (10(-8) M) during 6 days resulted in homologous desensitization of VIP receptor activity. Other peptides structurally related to the secretin-glucagon family, to neurotensin, or to gastrin are either ineffective or very weak agonist (hpGRF). GIP or pancreatic glucagon are inactive on the human colonic cell line HT-29, indicating the gastric specificity of the effect of GIP and glucagon in transformed epithelial cells originating from the human gastrointestinal tract. This implies that GIP and (pancreatic-entero) glucagon peptides may regulate gastric secretions directly, under similar mechanisms that those we evidenced in the rat.
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PMID:Gastric inhibitory peptide (GIP), pancreatic glucagon and vasoactive intestinal peptide (VIP) are cAMP-inducing hormones in the human gastric cancer cell line HGT-1. Homologous desensitization of VIP receptor activity. 632 77

A human glucagon-like 1 peptide receptor has been cloned from the gastric tumor cell line HGT-1. The cDNA clone encodes a protein of 463 amino acids and is a member of the superfamily of seven transmembrane domain G protein coupled receptors. Transfection of the human GLP-1 receptor into COS-7 cells confers upon them high affinity binding for [125I] GLP-1 (7-36) amide. In membranes prepared from COS-7 cells transfected with the human GLP-1 receptor, the binding of [125I] GLP-1 (7-36) amide is inhibited with the rank order of potency GLP-1 (7-36) amide > glucagon > secretin, characteristic of a GLP-1 receptor. The human GLP-1 receptor is functionally coupled to increases in intracellular cAMP in these cells: incubation of COS-7 cells expressing the human GLP-1 receptor with GLP-1 (7-36) amide gives rise to a 4-fold increase in cyclic AMP over basal levels, with an EC50 of 25pM. Glucagon is also a full agonist but is 200-fold less potent than GLP-1 (7-36) amide in stimulating the human GLP-1 receptor.
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PMID:Cloning and functional expression of a human glucagon-like peptide-1 receptor. 821 85

The HGT-1 gastric cancer cell line was used to determine the actions of protein kinase C on the stimulation of adenylate cyclase by the human histamine H2 receptor, and the receptors for gastric inhibitory polypeptide and truncated glucagon like peptide 1 (TGLP-1). Suspensions of HGT-1 cells were preincubated with the activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nmol/l), for 10 minutes. The subsequent cyclic adenosine monophosphate (AMP) response to 0.5 mmol/l histamine or 100 nmol/l TGLP-1 was reduced by comparison with control cells preincubated in the absence of TPA. The cyclic AMP response to 100 nmol/l gastric inhibitory polypeptide was enhanced by preincubation with TPA, while the responses to cholera toxin and forskolin were unaffected. Preincubation with pertussis toxin prevented the enhancement of the gastric inhibitory polypeptide response by TPA, suggesting an involvement of an inhibitory guanine nucleotide regulatory subunit of the Gi class, but did not change the inhibition of histamine stimulation. In conclusion, activation of protein kinase C produces a specific inhibition of the effects of histamine and TGLP-1 on adenylate cyclase activity in a human gastric cancer cell line by acting at a site close to their receptors.
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PMID:Protein kinase C inhibits cyclic adenosine monophosphate generation by histamine and truncated glucagon like peptide 1 in the human gastric cancer cell line HGT-1. 839 30