COMBINED EFFECT OF ADENOSINE, ALPHA-ADRENERGIC AND ADENOSINE ANTAGONISTS ON SERUM-INSULIN AND INSULIN-SECRETION FROM RAT PANCREATIC-ISLETS

1. The effect of adenosine separately or in combination with alpha-1 a drenergic antagonist prazosin and alpha-2 adrenergic antagonist yohimb ine as well as adenosine antagonists 8-phenyltheophylline and xanthine amine conjugate on glucose-induced insulin secretion from isolated ra t pancreatic islets was studied.2. Their in vivo effects on serum gluc ose and insulin levels were also investigated. Adenosine at 10 and 100 muM inhibited significantly, insulin secretion from the isolated isle ts whereas at 10 mM slightly increased the secretion of insulin. 3. Pr azosin used at 100 muM inhibited insulin secretion. When it combined w ith adenosine (10 muM) it augmented the inhibitory effect of adenosine . 4. In vivo prazosin (21 mg/kg body wt) caused a hyperglycaemia which was accompanied by hypoinsulinaemia. 5. Concurrent administration of this drug with adenosine neither affect the hyperglycaemic nor the hyp oinsulinaemic effects of adenosine. 6. On the other hand, yohimbine (1 00 muM) has no effect neither separately nor in combination with adeno sine (10 muM) in modulating the inhibitory effect of adenosine on insu lin secretion. 7. When Yohimbine administered at 19.5 mg/kg body wt it did not alter serum glucose but it markedly increased the serum insul in level. Its combined administration with adenosine reduced the hyper glycaemic effect of adenosine with a remarkable increase in serum insu lin. 8. Both adenosine-antagonists were ineffective in alteration of i nsulin secretion. 9. However, combination of 8-phenyltheophylline with adenosine (10 muM) totally blocked the inhibitory effect of adenosine on insulin secretion while xanthine amine conjugate failed to prevent this effect of adenosine. 10. These results indicate that the inhibit ory effect of adenosine on insulin secretion is neither mediated via a lpha-1 nor alpha-2 adrenoceptors. It might be via activation of specif ic adenosine receptors on rat islets which are sensitive to blockade b y 8-phenyltheophylline.