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 alpha 2-antagonist efaroxan in rat islets of Langerhans. alpha 2-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.