Interactions between calcium channel compounds and adenosine systems in brain of rat

Abstract

A number of organic ligands of calcium channels were investigated for possible actions on several aspects of adenosine systems in the cerebral cortex of rat. The principle findings of the present study were that a number of antagonists of calcium channels and the agonist compound Bay K 8644 inhibited binding to adenosine receptors, binding to nucleoside transporters, and the accumulation of [3H]adenosine with a low microM potency. 2-Nitrophenyl dihydropyridine derivatives were more potent than 3-nitrophenyl dihydropyridine or non-dihydropyridine ligands of calcium channels at inhibiting binding to adenosine receptors. Dihydropyridine ligands of calcium channels were more potent than non-dihydropyridine ligands of calcium channel in inhibiting the binding of [3H]nitrobenzylthioinosine to cortical membranes or inhibiting the accumulation of [3H]adenosine into synaptoneurosomes. However, unlike the case of adenosine receptors, no distinction between 2-nitrophenyl and 3-nitrophenyl dihydropyridine derivatives was observed. In addition, the non-dihydropyridine ligand of calcium channels, diltiazem was a weak inhibitor of the accumulation of [3H]adenosine. These results demonstrate that organic ligands of calcium channels, particularly dihydropyridine compounds, can interact with several aspects of adenosine systems.