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.
Chan
S L
SL
Department of Biological Sciences, Keele University, Staffs, UK.
Brown
C A
CA
Morgan
N G
NG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D007093:Imidazoles; D007328:Insulin; C062597:efaroxan