Delineation of the distribution of β-adrenergic receptor subtypes in canine myocardium

Abstract

β2-Receptors constitute only 10-30% of the total β-adrenergic receptors in mammalian ventricular myocardium, but their precise tissue location cannot be determined easily by measuring physiological variables. To delineate the distribution of β-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 β1-selective antagonist betaxolol or the β2-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 β1- and 25% were β2-receptors. The relative proportions of β-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 < 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% β1- and 15% β2-sites. In contrast, arterioles contained almost exclusively the β2-subtype. The diameters of coronary vessels in which β2-receptors were found to be selectively increased fell within a narrow range (mean ± SD, 35 ±11 μm; range, 16-55 μm). Small mural arteries and venules did not contain a significantly higher proportion of β2-receptors than adjacent myocytic regions.