STIMULATION OF INSULIN-SECRETION BY THE IMIDAZOLINE ALPHA-2-ADRENOCEPTOR ANTAGONIST EFAROXAN IS MEDIATED BY A NOVEL, STEREOSELECTIVE, BINDING-SITE

We have studied the stereospecificity of three responses mediated by the alpha2-antagonist efaroxan in rat islets of Langerhans. alpha2-Adrenergic inhibition of insulin secretion was relieved most effectively by the ( + ) enantiomer. In contrast, direct stimulation of insulin secretion and antagonism of the inhibitory effects of diazoxide were both preferentially mediated by the ( - ) enantiomer. Culture of islets in the presence of efaroxan resulted in loss of responsiveness to subsequent re-addition of the drug. On the basis of these results we propose the existence, in islets, of a novel 'non-adrenergic' binding site at which efaroxan acts as an agonist.