title: Effects of benextramine on the adrenergic inhibition of insulin secretion in isolated rat pancreatic islets.
abstract: Insulin secretion from isolated rat islets of Langerhans in the presence of 4 mM glucose averaged 2.26 +/- 0.20 (S.E.M.) ng/islet per 90 min and was significantly (P less than 0.001; n = 30) increased to 3.28 +/- 0.21 ng/islet per 90 min by the covalent alpha-adrenoceptor antagonist benextramine (10 microM). Glucose (20 mM) also increased the secretion rate (to 6.24 +/- 6.0 ng/islet per 90 min) but, under these conditions, the response was not further enhanced by benextramine. Clonidine and noradrenaline (1 nM-10 microM) each caused dose-dependent inhibition of glucose-induced insulin secretion which was maximal at 1 microM. Benextramine, when added simultaneously with the agonist, relieved, in a dose-dependent manner, the inhibition of secretion induced by either clonidine or noradrenaline with similar sensitivity. Even after a 30-min preincubation with benextramine the antagonist failed to differentiate between noradrenaline, adrenaline and clonidine with respect to inhibition of insulin secretion. In contrast to its effects on adrenergic responses, short-term treatment with benextramine did not significantly affect muscarinic-cholinergic receptor-mediated 45Ca2+ efflux from rat islets of Langerhans perifused in Ca2+-depleted medium. These data suggest that benextramine does not differentiate between clonidine and noradrenaline in rat islets of Langerhans but that it does show preference for alpha-adrenoceptors in this tissue.
authors.affiliation: Department of Biological Sciences, University of Keele, Staffordshire.
authors.forename: R D
authors.initials: RD
authors.lastname: Hurst
authors.forename: S L
authors.initials: SL
authors.lastname: Chan
authors.forename: N G
authors.initials: NG
authors.lastname: Morgan
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002469:Cell Separation; D003000:Clonidine / Q000494:pharmacology; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D000317:Adrenergic alpha-Antagonists; D007328:Insulin; C029998:benextramine; D002217:Carbachol; D005947:Glucose; D003000:Clonidine; D003538:Cystamine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine