[3H]R-terazosin binds selectively to alpha1-adrenoceptors over alpha2-adrenoceptors - comparison with racemic [3H]terazosin and [3H]prazosin

• Published in: European journal of pharmacology Vol. 327; no. 1; pp. 79 - 86
• Main Authors: Ireland, L M, Cain, J C, Rotert, G, Thomas, S, Shoghi, S, Hancock, A A, Kerwin, Jr, J F
• Format: Journal Article
• Language: English
• Published: Netherlands 26.05.1997
• Subjects: Adrenergic alpha-Antagonists - metabolism; Animals; Cricetinae; Humans; Mice; Prazosin - analogs & derivatives; Prazosin - metabolism; Radioligand Assay; Rats; Receptors, Adrenergic, alpha-1 - metabolism; Receptors, Adrenergic, alpha-2 - metabolism; Stereoisomerism
• ISSN: 0014-2999; 1879-0712

Most tissue sources for adrenoceptors contain a mixed population of alpha1- and/or alpha2-adrenoceptor subtypes; thus studies using non-specific radioligands are complicated by receptor heterogeneity. The examination of alpha1-adrenoceptor radioligand binding by radiolabeled terazosin and its enantiomers was simplified by using mouse fibroblast cells, which are thymidine kinase mutant (LTK-), transfected with cloned alpha1a-, alpha1b-, and alpha1d-adrenoceptor subtypes. [3H]Terazosin and its enantiomers were equipotent at the alpha1b-adrenoceptor. [3H]R-Terazosin was significantly less potent than [3H]terazosin and [3H]S-terazosin at the alpha1a- and the alpha1d-adrenoceptors. Using tissue derived alpha-adrenoceptors prepared in cold 25 mM glycyl-glycine buffer, [3H]prazosin, [3H]terazosin and [3H]S-terazosin bound to two sites in the rat neonatal lung preparation consistent with the presence of both alpha1- and alpha2B-adrenoceptors. The relative binding potencies of these radioligands at these two sites correlated with low affinity binding to the alpha2B-adrenoceptor and high affinity binding to an alpha1-adrenoceptor. [3H]R-Terazosin, on the other hand, bound to a single site in the rat neonatal lung membrane preparation, most likely an alpha1-adrenoceptor. Thus, [3H]R-terazosin may be useful as a selective alpha1-adrenoceptor radioligand for establishing the functional role of adrenoceptors in tissues expressing multiple subtypes.