Influence of thiol groups, calcium, and glucose metabolism on cholinergic-induced insulin release and on methylscopolamine binding to muscarinic receptors in pancreatic islets of the rat.
Short-term regulation of [3H]methylscopolamine binding to muscarinic receptors and acetylcholine-induced stimulation of insulin release was investigated in pancreatic islets of the rat. Binding of methylscopolamine was reversible; 47% of label was displaced 10 min and 70% 30 min after addition of unlabelled substance. 0.1 mM chloromercuribenzoic acid, when present during binding incubations, inhibited binding by 54%, whereas acetylcholine-induced insulin release was unaffected by the presence of the thiol reactant. Pre-incubation for 60 min in a calcium-deprived medium or in the presence of 50 microM trifluoroperazine likewise inhibited binding. Pre-incubation with 1.0 mM 3-isobutyl-l-methylxanthine or 16.7 M glucose failed to influence subsequent binding although acetylcholine-induced insulin release was 4-fold enhanced by priming with glucose. We conclude that 1) binding to muscarinic receptors is influenced by thiol interaction, 2) short-term alterations in calcium fluxes influence binding, whereas short-term changes in cyclic AMP (cAMP) or glucose metabolism do not, 3) a priming effect of glucose on insulin secretion is not mediated by changes in receptor binding.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002729:Chloromercuribenzoates / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology; D020245:p-Chloromercuribenzoic Acid
D002729:Chloromercuribenzoates; D007328:Insulin; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D013438:Sulfhydryl Compounds; D014268:Trifluoperazine; D020245:p-Chloromercuribenzoic Acid; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D019832:N-Methylscopolamine