EFFECTS OF IMIDAZOLINE ANTAGONISTS OF ALPHA(2)-ADRENOCEPTORS ON ENDOGENOUS ADRENALINE-INDUCED INHIBITION OF INSULIN RELEASE

We studied the effects of adrenoceptor antagonists and imidazoline der ivatives on endogenous adrenaline-induced inhibition of insulin releas e in anesthetized rats. The intracerebroventricular injection of neost igmine increased plasma levels of catecholamines and glucose but not i nsulin. Pretreatment with an i.p. injection with phentolamine caused a dose-dependent increase in insulin secretion. When atropine was coadm inistered with phentolamine, the phentolamine-induced increase in insu lin secretion was inhibited. Neither phentolamine nor atropine affecte d plasma levels of catecholamine. Yohimbine and idazoxan, which are al pha(2)-adrenoceptor antagonists, and tolazoline, a non-selective alpha -adrenoceptor antagonist, also reversed adrenaline-induced inhibition of insulin secretion. Phenoxybenzamine, prazosin, propranolol, and ant azoline, an imidazoline without alpha(2)-adrenoceptor activity, did no t affect insulin levels. When agents were preinjected i.p. in rats tha t were given saline into the third cerebral ventricle, phentolamine an d antazoline, but not yohimbine and idazoxan, increased plasma levels of insulin. The results suggest that the inhibition of insulin release induced by adrenaline was reversed by antagonism of alpha(2)-adrenoce ptors. Phentolamine and antazoline, both of which are imidazoline deri vatives, induced insulin secretion independently of the adrenoceptors only under the resting conditions.