title: Comparison of cloned and pharmacologically defined rat tissue alpha 1-adrenoceptor subtypes.
abstract: Multiple alpha 1-adrenoceptor subtypes have been defined by pharmacological and receptor cloning techniques, but the precise alignment of cloned and pharmacologically-defined subtypes is still unclear. We have compared the affinities of 8 subtype-selective compounds at three cloned alpha 1-adrenoceptor subtypes (rat alpha 1B, bovine alpha 1C, rat alpha 1A/D) with those previously determined by the same methods in rat spleen, cerebral cortex, and kidney (Naunyn-Schmiedeberg's Arch. Pharmacol. 348: 385-395, 1993). Among all compounds tested to date at cloned alpha 1-adrenoceptor subtypes (+)-tamsulosin appears to be the most selective with a rank order of potency alpha 1C > alpha 1A/D > or = alpha 1B. Affinities for the alpha 1A-selective 5-methyl-urapidil, methoxamine, oxymetazoline, phentolamine and (-)- and (+)-tamsulosin and for noradrenaline and SDZ NVI-085 at the splenic alpha 1B-adrenoceptors and at their low affinity sites in cerebral cortex and kidney correlated best with those at the cloned alpha 1B-adrenoceptor. Affinities of these drugs at their high affinity sites in cerebral cortex (pharmacologically-defined alpha 1A-adrenoceptor) were matched best by those at the cloned alpha 1C-adrenoceptor. Rat kidney appears to contain two chloroethylclonidine-resistant alpha 1-adrenoceptor subtypes one of which is similar to the cloned alpha 1C- and one to the cloned alpha 1A/D-adrenoceptor. We conclude that the cloned alpha 1B-adrenoceptor is the genetic correlate of the pharmacologically-defined alpha 1B-adrenoceptor. An alpha 1-adrenoceptor subtype corresponding to the cloned alpha 1A/D-adrenoceptor appears to exist in rat kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Essen, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
authors.forename: P A
authors.initials: PA
authors.lastname: Insel
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003001:Cloning, Molecular; D011224:Prazosin / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism; D000077409:Tamsulosin
chemical_list: D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D000077409:Tamsulosin; D011224:Prazosin