NONHOMOGENEOUS DISTRIBUTION OF BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS IN VARIOUS HUMAN TISSUES

The distribution of beta1- and beta2-adrenoceptor subtypes was determined in membranes obtained from the right atrium, abdominal fat pad, kidney, lung and liver of each of three human subjects. The number of each beta-adrenoceptor subtype was calculated by nonlinear least-squares computer analysis of the competition curve of (-) [I-125] iodocyanopindolol (I-125-CYP) binding, using beta1-selective antagonist CGP 20712A and beta2-selective antagonist ICI 118,551. Competition studies using CGP 20712A indicated that both 81- and 82-adrenoceptor subtypes coexist in all five tissues, with marked difference in the relative proportion of beta1- and beta2-adrenoceptors among these tissues. Most notably, the existence of beta1-subtypes could be clearly shown in the lung (275) and liver (18%); acoording to previous reports, beta2-subtypes are found almost exclusively in the lung and liver in humans. Regarding the kidney, the present results (beta2-subtypes: 68%) also differed from previous human data in that beta1-subtypes predominated. Consistent results were obtained in experiments with ICI 118,551. These results provide a new insight into the mechanism by which catecholamines regulate a particular beta-adrenergic function in these tissues.