Dihydropyridines alter adenosine sensitivity in the rat hippocampal slice.

1. The effects of adenosine and a range of adenosine analogues, which are resistant to uptake processes, were studied in the presence of dihydropyridines and verapamil on the population spike potential recorded from the CA1 area of the hippocampal slice. 2. Nifedipine and Bay K 8644, a calcium channel antagonist and activator respectively, enhanced the inhibitory action of adenosine in a concentration-dependent manner. This was in contrast to their effect on adenosine analogues where the inhibition of the population potential was significantly attenuated. Similar interactions between the adenosine compounds and the dihydropyridines were also displayed in studies on spontaneous epileptiform activity in the CA3 region. 3. This effect of nifedipine and Bay K 8644 was not shown by the dihydropyridines, nimodipine or nitrendipine, or by the phenylalkylamine, verapamil. 4. Addition of the adenosine uptake blocker dipyridamole reversed the action of nifedipine on adenosine, so that inhibition by adenosine was now attenuated by nifedipine in a similar manner to that observed with the adenosine analogues. 5. These results can be explained with reference to binding studies that show displacement of adenosine analogues from the adenosine receptor by dihydropyridines. An action at the adenosine uptake site by the dihydropyridines explains the enhancement of adenosine inhibition. 6. The possible sites for this interaction are discussed.