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)

Cholinergic agents are potent modulators of insulin release that act via muscarinic receptors. We now investigated the muscarinic receptor subtype present in rat pancreatic islets in binding and functional studies. Binding of 5 nM [3H]N-methylscopolamine ([3H]NMS) was half maximal at 30 min. At 60 min, the maximal total binding was 1.29% and the non-specific binding (presence of 100 microM atropine) was 0.18% of the total radioactivity per 10 micrograms islet protein. Unlabelled atropine inhibited [3H]NMS binding with an IC50 of ca. 30 nM. The rank order of antagonist high-affinity binding was atropine greater than sila-hexocyclium methyl sulfate (SiHC; M1 greater than M3 greater than M2) greater than pirenzepine (M1 greater than M2 approximately M3) = methoctramine (M2 greater than M1 greater than M3). The high-affinity Kds were 8.5, 56, 1300 and 1300 nM, respectively. The high affinity Kd of the muscarinic receptor agonist, arecaidine propargyl ester (APE), was 8.1 nM. The EC50 for the biological effects of APE on insulin and glucagon secretion was 3.2 and 2.3 nM. The rank order for the high-affinity biological effects of antagonists (inhibition of APE-mediated insulin/glucagon release) was almost the same as for binding. The data indicate that rat pancreatic islets contain neither an M1 subtype (high-affinity for pirenzepine) nor an M2 subtype (high-affinity for methoctramine) receptor. However, the data evidence an M3 receptor subtype, since SiHC in the absence of the M1 receptor subtype shows a relatively high affinity to the receptors in rat pancreatic islets.
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PMID:Muscarinic receptor subtypes in rat pancreatic islets: binding and functional studies. 218 4

Studies on the cholinergic regulation of intestinal L-cells have been focused on the release of enteroglucagon, but the signal transduction pathways were not defined. These were here investigated by using as index the release of immunoreactive glucagon-like peptide-1 (GLP-1) from the endocrine cell line STC-1, that has been shown to contain proglucagon mRNA transcripts. Abundant GLP-1 immunoreactivity was revealed in STC-1 cells at immunocytochemistry and by RIA. The cell content was 4927 +/- 689 pg/10(6) cells, as measured with antiserum 199D that recognizes specifically the C-terminal amidated forms of GLP-1. The secretion of GLP-1 over a 2-h incubation period amounted to 1.4 +/- 0.3% of the total GLP-1 cell content and was significantly increased by 10 microM forskolin and 100 nM 12-O-tetradecanoylphorbol 13-acetate to 206% and 574% of control values, respectively. The cholinergic agonist carbachol stimulated GLP-1 secretion in a concentration-dependent manner, maximal release was observed at 1 mM carbachol (228% of the control value). Binding of the muscarinic antagonist [N-methyl-]scopolamine ([3H]NMS) on cell homogenates was time dependent, specific, and saturable. Scatchard analysis revealed one class of receptors (Kd, 14 pM; binding capacity, 20 fmol/mg protein). Carbachol (0.1 microM to 1 mM) dose dependently displaced [3H] NMS binding and increased the intracellular calcium concentration without modification of adenylate cyclase activity. The order of potency of different antagonists, showing a preferential affinity for M1, M2, and M3 muscarinic receptor subtypes, to inhibit [3H]NMS binding, the carbachol-induced increase in intracellular calcium, and carbachol-stimulated GLP-1 secretion, was as follows: atropine (nonselective) > 4-diphenylacetoxy-N-methylpiperidine methiodide (M3) > pirenzepine (M1) > AF-DX 116 (M2). The results of the present study, therefore, demonstrate that secretion of GLP-1 induced by cholinergic agonist depends on muscarinic M3-subtype receptors in the endocrine intestinal cell line STC-1. This system may prove useful to study the cellular mechanisms of GLP-1 secretion.
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PMID:Stimulation of glucagon-like peptide-1 secretion by muscarinic agonist in a murine intestinal endocrine cell line. 815 1