Dihydropyridine Ca2+ entry blockers selectively inhibit peak I cAMP phosphodiesterase.
The vasodilatory action of Ca2+ entry blockers is due primarily to slow Ca2+ channel inhibition; however, these drugs may have additional sites of action that contribute to vasodilation. Eleven Ca2+ entry blockers were evaluated for their inhibition of the two major forms of bovine heart cAMP phosphodiesterase which were separated by DEAE cellulose chromatography. Nifedipine and four other dihydropyridine Ca2+ entry blockers selectively inhibited peak I phosphodiesterase activity with IC50 values between 2 and 3 microM but were weak inhibitors of peak II phosphodiesterase with IC50 values of 100 microM or greater. The selective inhibition of peak I phosphodiesterase activity by these dihydropyridine Ca2+ entry blockers may be an intracellular mechanism for producing vasodilation in addition to slow Ca2+ channel inhibition.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D002848:Chromatography, DEAE-Cellulose; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D009543:Nifedipine