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 channel antagonists, namely verapamil (CAS 52-53-9) and nifedipine (CAS 21829-25-4) in modifying the inhibitory influence of adenosine on insulin secretion from isolated rat pancreatic islets. The combined effect of adenosine and these agents on serum insulin and glucose levels in vivo was also investigated. Both verapamil and nifedipine at 100 mumol/l and 1 mumol/l, respectively, produced a significant inhibition of glucose-stimulated insulin secretion from pancreatic islets. Combination of these agents with adenosine 10 mumol/l did not modify the inhibitory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b.wt.) and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prior to glucose loading produced a significant increase in serum glucose with an accompanied decrease in serum insulin levels. Concurrent administration of verapamil with adenosine neither affected the hyperglycaemic nor the hypoinsulinaemic effects of adenosine, whereas combined administration of nifedipine and adenosine decreased the hyperglycaemic effect of adenosine but not its hypoinsulinaemic effect. These results may indicate that these calcium channel antagonists do not interact with adenosine receptors which mediate its inhibitory effect on insulin secretion.