Delineation of the distribution of beta-adrenergic receptor subtypes in canine myocardium.

Abstract

beta 2-Receptors constitute only 10-30% of the total beta-adrenergic receptors in mammalian ventricular myocardium, but their precise tissue location cannot be determined easily by measuring physiological variables. To delineate the distribution of beta-receptor subtypes in myocytic and vascular components of the heart, we incubated transmural sections of canine left ventricle with [125Iodo]cyanopindolol and selected concentrations of the beta 1-selective antagonist betaxolol or the beta 2-selective antagonist ICI 118,551. Detailed competition binding data were best accounted for by a two-site model in which approximately 75% of total sites were beta 1- and 25% were beta 2-receptors. The relative proportions of beta-receptor subtypes in myocytic and vascular components were assessed autoradiographically by analyzing the density of binding sites in transmural sections incubated with radioligand and subtype-selective displacers. Betaxolol (10(-7) M) reduced the density of radioligand binding sites by 44% in regions composed primarily of ventricular myocytes but by less than 5% in small coronary arterioles. ICI 118,551 (10(-7) M) reduced radioligand binding-site density by 18% in myocytic regions and by 55% in small arterioles. In myocytic regions, these data indicated a subtype composition of approximately 85% beta 1- and 15% beta 2-sites. In contrast, arterioles contained almost exclusively the beta 2-subtype. The diameters of coronary vessels in which beta 2-receptors were found to be selectively increased fell within a narrow range (mean +/- SD, 35 +/- 11 microns; range, 16-55 microns). Small mural arteries and venules did not contain a significantly higher proportion of beta 2-receptors than adjacent myocytic regions.