Binding properties of beta-blockers at recombinant beta(1)-, beta(2)-, andbeta(3)-adrenoceptors

The human heart contains at least four distinct beta-adrenoceptor subtypes, three of which have been cloned. However, the binding properties of beta-b lockers to the different beta-adrenoceptor subpopulations are not yet thoro ughly characterized. Human beta(1)-, beta(2)- and beta(3)-adrenoceptors wer e expressed in COS-7 cells and [I-125]iodocyanopindolol saturation binding, and competition experiments with commonly used beta-blockers were performe d in the respective membrane preparations. Atenolol and metoprolol were abo ut fivefold selective for beta(1)- versus beta(2)- and beta(3)-adrenoceptor s. Bisoprolol was similar to 15-fold selective for beta(1)- versus beta(2)- and similar to 31-fold selective for beta(1)- versus beta(3)-adrenoceptors . Carvedilol was nonselective for any beta-adrenoceptor subtype. We conclud e that the beta(1)-selectivities of atenolol, metoprolol, and bisoprolol ar e lower in COS cell membranes compared with previous investigations perform ed in native membranes. All beta-blockers investigated bind to beta(3)-adre noceptors. Differential binding properties to beta(3)-adrenoceptors might i mply different responses as to body weight, cardiac contractility, heart ra te, and growth regulation. This might imply differential indications for th e drugs investigated.