EFFECT OF CALCIUM-CHANNEL ANTAGONISTS IN MODIFYING THE INHIBITORY INFLUENCE OF ADENOSINE ON INSULIN-SECRETION

The present work was performed to study the effect of two calcium chan nel antagonists, namely verapamil (GAS 52-53-9) and nifedipine (GAS 21 829-25-4) in modifying the inhibitory influence of adenosine on insuli n secretion fr om isolated rat pancreatic islets. The combined effect of adenosine and these agents on serum insulin and glucose levels in v ivo was also investigated. Both verapamil and nifedipine at 100 mu mol /l and mu mol/l, respectively, produced a significant inhibition of gl ucose-stimulated insulin secretion fi om pancreatic islets. Combinatio n of these agents with adenosine 10 mu mol/l did not modify the inhibi tory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b .wt.) and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prio r to glucose loading produced a significant increase in serum glucose with an accompanied decrease in serum insulin levels. Concurrent admin istration of verapamil with adenosine neither affected the hyperglycae mic nor the hypoinsulinaemic effects of adenosine, whereas combined ad ministration of nifedipine and adenosine deer-eased the hyperglycaemic effect of adenosine bur not its hypoinsulinaemic effect. These result s may indicate that these calcium channel antagonists do not interact with adenosine receptors which mediate its inhibitory effect on insuli n secretion.