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Quantitative analysis of beta-adrenergic receptor subtypes in pig tissues.

The density and distribution of beta1- and beta2-adrenergic receptors (betaAR) in porcine adipocytes, skeletal muscle, heart, lung, and liver were investigated using competitive displacement of ligand binding with subtype-selective ligands. Three experimental approaches were used to estimate the distribution of betaAR subtypes in adipocytes. Two approaches involved simultaneous linear regression analysis of multiple competitive displacement curves with the beta1AR-selective antagonist CGP 20712A and the beta2AR-selective ligand BRL 37344. For the third approach, radioligand saturation assays were perfomed using a concentration of CGP 20712A that completely blocked the beta1AR. All three approaches indicated the presence of multiple betaAR subtypes in porcine adipocytes and gave similar estimates for the proportion of these subtypes. Saturation assays in the presence of the beta1AR blocker CGP 20712A were conducted to determine the distribution of the betaAR subtypes in skeletal muscle, heart, lung, and liver. The proportions of the beta1AR and beta2AR were 81:19, 59:41, 72:28, 58:42, and 50:50 for adipose, skeletal muscle, heart, lung, and liver, respectively. These estimates based on receptor protein were consistent with published estimates of mRNA abundance in pig tissues but differ from estimates for other species. The predominance of beta1AR in adipocytes and skeletal muscle may contribute to the reduced efficacy of select betaAR agonists in pigs compared to other species because most of the ligands evaluated in growth studies are purported to be beta2AR selective. The density of the betaAR varied among tissues in the following order: heart = lung > adipocytes > skeletal muscle or = liver.