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Human cardiac beta-adrenoceptors: both beta 1- and beta 2-adrenoceptors are functionally coupled to the adenylate cyclase in right atrium.

We investigated properties of catecholamine-sensitive adenylate cyclase in membranes from human right atria. Basal adenylate cyclase was activated by Mg2+-ions and guanyl nucleotides [Gpp(NH)p, GTP] in a concentration-dependent manner; guanyl nucleotide activation was strongly dependent on the presence of Mg2+-ions. Catecholamines stimulated adenylate cyclase activity in the following order of potency: (-)-isoprenaline greater than (-)-adrenaline = (-)-noradrenaline greater than phenylephrine, indicating that, in human right atrium, beta 1-adrenoceptors predominate. The beta 1-agonist dobutamine and the beta 2-agonists fenoterol and procaterol activated adenylate cyclase with an intrinsic activity of 0.5-0.7 (isoprenaline = 1.0). Adenylate cyclase activation by dobutamine or procaterol was not additive with the activation induced by isoprenaline. On the contrary, combination of dobutamine (100 microM) and procaterol (10 microM) resulted in activation of adenylate cyclase which was not different from that evoked by saturating concentration of isoprenaline (10 microM), indicating that dobutamine (beta 1) and procaterol (beta 2) produce adenylate cyclase activation through stimulation of different beta-adrenoceptor subtypes. The beta 2-selective antagonist ICI 118,551 was much more potent in inhibiting procaterol-than isoprenaline-stimulated adenylate cyclase activity, whereas the beta 1-selective antagonist betaxolol inhibited isoprenaline-stimulated activity more potently. We conclude that in human right atrium, both beta 1- and beta 2-adrenoceptors are functionally coupled to the adenylate cyclase system.