Coexistence of β1 and β2-Adrenoceptors in the Rabbit Heart

Abstract

Summary We determined the amount of β₁ and β₂-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-³H-dihydroalprenolol [(-)-³H-DHA] binding (5 nM) by β₁-selective (practolol, metoprolol) and β₂-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective β-adrenergic drugs resulted in nonlinear Hofstee plots, suggesting the coexistence of both β-adrenoceptor subtypes. From these plots we calculated a β₁:β₂-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of β₂-adrenoceptors (approximately 5–7% of the total β-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-³H-DHA binding in tissues with homogeneous population of β-adrenoceptors (β₁:guinea pig left ventricle; β₂:cerebellum of mature rats). For both tissues the four selective β-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous β-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that β₁- and β₂-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed with β₁adrenoceptors.