Inhibitory effect of NZ-105, a 1,4-dihydropyridine derivative, on cyclic nucleotide phosphodiesterase activity

The effects of NZ-105, a 1,4-dihydropyridine calcium antagonist, on the intracellular cyclic nucleotide system were investigated in-vitro. In rabbit isolated aorta, both NZ-105 (1 and 10 microM) and nicardipine significantly and in a concentration-dependent manner increased intracellular cyclic AMP and cyclic GMP content. NZ-105 inhibited bovine cardiac phosphodiesterase activity (Ki 30 microM) by competitive antagonism. The concentration ranges for inhibition were consistent with the range of increases in cyclic nucleotides.