Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (-)-3H-dihydroalprenolol binding.
We determined the amount of beta 1- and beta 2-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-3H-dihydroalprenolol [(-)-3H-DHA] binding (5 nM) by beta 1-selective (practolol, metoprolol) and beta 2-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective beta-adrenergic drugs resulted in non-linear Hofstee plots, suggesting the coexistence of both beta-adrenoceptor subtypes. From these plots we calculated a beta 1:beta 2-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of beta 2-adrenoceptors (approximately 5-7% of the total beta-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-3H-DHA binding in tissues with homogeneous population of beta-adrenoceptors (beta 1:guinea pig left ventricle; beta 2: cerebellum of mature rats). For both tissues the four selective beta-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous beta-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that beta 1- and beta 2-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed the beta 1-adrenoceptors.
D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D001665:Binding Sites; D004082:Dihydroalprenolol / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000032:analysis*; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011941:Receptors, Adrenergic / Q000032:analysis*; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism; D014316:Tritium
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D004082:Dihydroalprenolol; D000526:Alprenolol