Binding properties of β-blockers at recombinant β1-, β2-, and β3-adrenoceptors

The human heart contains at least four distinct beta-adrenoceptor subtypes, three of which have been cloned. However, the binding properties of beta-blockers to the different beta-adrenoceptor subpopulations are not yet thoroughly characterized. Human beta(1)-, beta(2)- and beta(3)-adrenoceptors were expressed in COS-7 cells and [I-125]iodocyanopindolol saturation binding, and competition experiments with commonly used beta-blockers were performed in the respective membrane preparations. Atenolol and metoprolol were about fivefold selective for beta(1)- versus beta(2)- and beta(3)-adrenoceptors. 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 conclude that the beta(1)-selectivities of atenolol, metoprolol, and bisoprolol are lower in COS cell membranes compared with previous investigations performed in native membranes. All beta-blockers investigated bind to beta(3)-adrenoceptors. Differential binding properties to beta(3)-adrenoceptors might imply different responses as to body weight, cardiac contractility, heart rate, and growth regulation. This might imply differential indications for the drugs investigated.