Effects of benextramine on the adrenergic inhibition of insulin secretion in isolated rat pancreatic islets

Insulin secretion from isolated rat islets of Langer-hans in the presence of 4 mm glucose averaged 2\m=.\26\m=+-\0\m=.\20(s.e.m.) ng/islet per 90 min and was significantly (P<0\m=.\001; n=30) increased to 3\m=.\28\m=+-\0\m=.\21ng/islet per 90 min by the covalent \g=a\\x=req-\ adrenoceptor antagonist benextramine (10 \g=m\m). Glucose (20 mM) also increased the secretion rate (to 6\m=.\24\m=+-\6\m=.\0ng/islet per 90 min) but, under these con-ditions, the response was not further enhanced by benextramine. Clonidine and noradrenaline (1 nm\p=m-\ 10 \g=m\m)each caused dose-dependent inhibition of glucose-induced insulin secretion which was maximal at 1 \g=m\m.Benextramine, when added simul-taneously 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 preincuba-tion with benextramine the antagonist failed to differentiate between noradrenaline, adrenaline and clonidine with respect to inhibition of insulin secre-tion. In contrast to its effects on adrenergic re-sponses, short-term treatment with benextramine did not significantly affect muscarinic\p=m-\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 prefer-ence for \g=a\-adrenoceptorsin this tissue