Regional distribution of beta-adrenoceptors in the human heart: coexistence of functional beta 1- and beta 2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy.
We evaluated the amount of beta 1- and beta 2-adrenoceptors in human right and left atrium as well as in right and left ventricular wall obtained from heart transplant recipients who suffered from end-stage congestive cardiomyopathy. The total number of myocardial beta-adrenoceptors was assessed with the nonsubtype selective beta-adrenoceptor radioligand (-)[125I]iodocyanopindolol (ICYP); concomitantly, the number of beta 1-adrenoceptors was determined with the selective beta 1-adrenoceptor radioligand (-)[3H]bisoprolol. The number of beta 2-adrenoceptors was calculated by subtracting (-)[3H]bisoprolol binding sites from ICYP binding sites. With this technique, a beta 1/beta 2-ratio of approximately 65/35% for both atria and of approximately 75/25% for both ventricles was found. Identical results were obtained when the beta 1/beta 2-ratio was calculated indirectly by nonlinear regression analysis of competition curves of the selective beta 1-adrenoceptor antagonist bisoprolol and the selective beta 2-adrenoceptor antagonist ICI 118,551 with ICYP binding. In addition, on atria and on ventricles, adenylate cyclase was activated by norepinephrine (presumably by beta 1- and beta 2-adrenoceptor stimulation) and by procaterol (by beta 2-adrenoceptor stimulation). It is concluded that in the human heart functional beta 1- and beta 2-adrenoceptors coexist on both atria and both ventricles. In end-stage congestive cardiomyopathy, there appears to be a selective down-regulation of cardiac beta 1-adrenoceptors, whereas beta 2-adrenoceptors are obviously not affected. This may explain the beneficial effects of beta 2-adrenoceptor agonists in severe heart failure.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D020120:Iodocyanopindolol; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives; D017265:Procaterol; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D017265:Procaterol