title: Identification of alpha 1-adrenoceptor subtypes in the human prostatic urethra.
abstract: To identify the alpha 1-adrenoceptor subtypes in the human prostatic urethra, we compared the potencies of various alpha 1-adrenoceptor agonists and antagonists in inhibiting [3H]tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the binding of (+)-beta-([125I]iodo-4-hydroxyphenyl)ethylaminomethyl-tetralone ([125I]HEAT) to cloned human alpha 1a, alpha 1b and alpha 1d subtypes. The alpha 1A-selective antagonists 5-methylurapidil and (+)niguldipine showed higher affinities for both cloned alpha 1a and urethral alpha 1-adrenoceptors than for cloned alpha 1b- and alpha 1d-adrenoceptors. NS-49, (R)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, recently characterized as an alpha 1A-selective agonist, also showed high affinity for the cloned alpha 1a subtype and urethral alpha 1-adrenoceptors. Prazosin showed lower affinity for alpha 1-adrenoceptors in the human prostatic urethra than for any of the three cloned alpha 1-adrenoceptors. Comparison of the affinities of alpha 1-adrenoceptor agonists and antagonists for human prostatic urethral alpha 1-adrenoceptors to their affinities for the three cloned alpha 1 subtypes indicated a close correlation between the affinities for human urethral alpha 1 and the cloned alpha 1a-adrenoceptors. However, prazosin did not conform to this pattern. These findings suggest that the predominant alpha 1-adrenoceptor in the human urethra is the alpha 1A subtype, and that an alpha 1L subtype which has been characterised by its low affinity for prazosin, may also be present.
authors.affiliation: Nippon Shinyaku Co. Ltd., Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ukai
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: N
authors.initials: N
authors.lastname: Moriyama
authors.forename: K
authors.initials: K
authors.lastname: Kawabe
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000187:drug effects*; D011485:Protein Binding; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism; D000077409:Tamsulosin; D014521:Urethra / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D000077409:Tamsulosin