Abstract: | To determine whetherthe phosphoinositol/Ca2+ pathwayinteracts with the adenylate cyclase/adenosine 3',5'-cyclicmonophosphate (cAMP) pathway in the cardiac -receptor, the effectsof U-50488, a specific -receptor agonist, on the intracellularCa2+ concentration(Ca2+]i)and forskolin-induced accumulation of cAMP in rat ventricular myocyteswere determined after interference of thephosphoinositol/Ca2+ pathway.U-50488 suppressed the forskolin-induced accumulation of cAMP andelevatedCa2+]i,which were blocked by norbinaltorphimine, a specific -receptor antagonist, and pertussis toxin. The effects of U-50488 werequalitatively similar to those of A-23187, aCa2+ ionophore, but opposite tothose of1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester (AM), aCa2+]ichelator. Abolition of U-50488-induced elevation ofCa2+]iby BAPTA-AM also abolished the effect of U-50488 on forskolin-induced accumulation of cAMP. Inhibition of the phospholipase C by specific inhibitors, U-73122 and neomycin, abolished the effects of U-50488 onbothCa2+]iand forskolin-induced accumulation of cAMP. The results showed for thefirst time that -receptor stimulation may suppress cAMP accumulationvia activation of thephosphoinositol/Ca2+ pathway inthe rat heart. |