Distribution and function of beta-adrenoceptors in different chambers of the canine heart

Abstract

1 An improved binding assay involving (-)-[(3)H]-dihydroalprenolol (DHA) and KCl-washed cardiac membranes was developed to study beta-adrenoceptors in the canine heart quantitatively.2 Receptor numbers varied from 3.8 to 7.1 pmol/g fresh tissue, showing a steady increase from left atrium --> right atrium --> right ventricle --> interventricular septum --> left ventricle. With one minor exception, the same pattern was found for adenylate cyclase activity and Na(+), K(+)-activated ATPase activity.3 The binding of DHA was inhibited in the expected manner by beta-adrenoceptor agonists and antagonists, and was stereospecific, in confirmation of previous studies. Dissociation constants determined from Scatchard analyses included DHA: 2.5 nM; (-)adrenaline: 230 nM; (-)noradrenaline: 1167 nM. Kinetic analyses of the binding of DHA yielded a K(D) of about 4 nM.4 The distribution of beta-receptors is closely related to that of blood flow and the arrival plus retention of a circulating catecholamine, but is markedly different from that of endogenous noradrenaline, and thus adrenergic nerve terminals. Most receptors thus appear not at synapses but diffusely localized where they can react with circulating adrenaline.5 Evidence is discussed that beta-receptors at synapses respond primarily to neural noradrenaline, less to circulating adrenaline, and hardly at all to circulating noradrenaline; responses mediate increased cardiac output during exercise. In contrast most cardiac beta-receptors appear to respond only to adrenaline, and to be used, except at times of severe circulatory stress, during psychological stress.