Binding properties of beta-blockers at recombinant beta1-, beta2-, and beta3-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 beta1-, beta2- and beta3-adrenoceptors were expressed in COS-7 cells and [125I]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 beta1- versus beta2- and beta3-adrenoceptors. Bisoprolol was approximately 15-fold selective for beta1- versus beta2- and approximately 31-fold selective for beta1- versus beta3-adrenoceptors. Carvedilol was nonselective for any beta-adrenoceptor subtype. We conclude that the beta1-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 beta3-adrenoceptors. Differential binding properties to beta3-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.
Schnabel
P
P
Klinik III für Innere Medizin der Universität zu Köln, Cologne, Germany. Petra.Schnabel@uni-koeln.de
Maack
C
C
Mies
F
F
Tyroller
S
S
Scheer
A
A
Böhm
M
M
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D019556:COS Cells; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D020120:Iodocyanopindolol / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011869:Radioligand Assay; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000319:Adrenergic beta-Antagonists; D018076:DNA, Complementary; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D020120:Iodocyanopindolol