DILTIAZEM PREVENTS THE DEPRESSION OF ADENYLYL-CYCLASE ACTIVITY-INDUCED BY THE CALCIUM PARADOX IN RAT

In isolated rat hearts the calcium paradox, induced by perfusion for 3 minutes in the absence of calcium followed by perfusion for 10 minute s in the presence of calcium, depressed the activation of adenylyl cyc lase by 1-isoproterenol, NaF and forskolin. The characteristics of the beta-adrenoceptors and the activation of adenylyl cyclase by guanylyl imidodiphosphate were not changed. The findings suggest an uncoupling of beta-adrenoceptors from the catalytic site of the adenylate cyclas e complex. Diltiazem, at 0.4 muM in the perfusion medium, greatly redu ced the diminution of the activation of adenylate cyclase by isoproter enol and forskolin, and completely prevented the depression of the act ivation of adenylate cyclase by NaF. These effects may be due to inter ference by diltiazem with the mechanisms that promote an excessive inf lux of calcium into the heart during the calcium paradox.