Conditioning of beta(1)-adrenoceptor effect via beta(2)-subtype on L-type Ca2+ current in canine ventricular myocytes

We investigated the roles of beta(1)- and beta(2)-receptors (beta-AR) in ad renergic enhancement of L-type Ca2+ current (I-CaL) in canine ventricular m yocytes. Isoproterenol and l-norepinephrine produced a monophasic and a bip hasic concentration-I-CaL relationship (CR), respectively. alpha(1)-AR inhi bition with prazosin and beta(2)-AR stimulation with zinterol or l-epinephr ine shifted the CR of l-norepinephrine leftward. Zinterol (50 nM) and l-epi nephrine (10 nM), but not prazosin, altered the biphasic CR of l-norepineph rine to a monophasic CR. Zinterol and l-epinephrine applied after l-norepin ephrine had no effect on I-CaL. beta(2)-AR inhibition with ICI-118551 reduc ed the E-max of isoproterenol and l-norepinephrine by 60% and abolished the augmentation of l-norepinephrine by zinterol and l-epinephrine. Carbachol (100 nM) modestly reduced the I-CaL response to beta(1)-AR stimulation but abolished the enhancement via beta(2)-AR. Zinterol augmented the enhancemen t of I-CaL by forskolin, IBMX, and theophylline, but not in the presence of CGP-20712A. We conclude that selective beta(2)-AR stimulation does not inc rease I-CaL but enhances adenylyl cyclase activity when stimulated via beta (1)-AR and with forskolin. beta(2)-AR activity preconditions adenylyl cycla se for beta(1)-AR stimulation.