title: [3H]R-terazosin binds selectively to alpha1-adrenoceptors over alpha2-adrenoceptors - comparison with racemic [3H]terazosin and [3H]prazosin.
abstract: 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.
authors.affiliation: Abbott Laboratories, Department 4MN, Abbott Park, IL 60064-3500, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Ireland
authors.forename: J C
authors.initials: JC
authors.lastname: Cain
authors.forename: G
authors.initials: G
authors.lastname: Rotert
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Shoghi
authors.forename: A A
authors.initials: AA
authors.lastname: Hancock
authors.forename: J F
authors.initials: JF
authors.lastname: Kerwin
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D006224:Cricetinae; D006801:Humans; D051379:Mice; D011224:Prazosin / Q000031:analogs & derivatives* / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; C041226:Terazosin; D011224:Prazosin