Comparison of cloned and pharmacologically defined rat tissue α1-adrenoceptor subtypes

Abstract

Multiple α1-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 α1-adrenoceptor subtypes (rat α1B, bovine α1C rat α1A/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 α1-adrenoceptor subtypes (+)-tamsulosin appears to be the most selective with a rank order of potency α1C > α1A/D ≥ α1B. Affinities for the α1A-selective 5-methyl-urapidil, methoxamine, oxymetazoline, phentolamine and (-)- and (+)-tamsulosin and for noradrenaline and SDZ NVI-085 at the splenic α1B-adrenoceptors and at their low affinity sites in cerebral cortex and kidney correlated best with those at the cloned α1B-adrenoceptor. Affinities of these drugs at their high affinity sites in cerebral cortex (pharmacologically-defined α1A-adrenoceptor) were matched best by those at the cloned α1C-adrenoceptor. Rat kidney appears to contain two chloroethylclonidine-resistant α1-adrenoceptor subtypes one of which is similar to the cloned at α1C- and one to the cloned α1A/D-adrenoceptor. We conclude that the cloned α1B-adrenoceptor is the genetic correlate of the pharmacologically-defined α1B-adrenoceptor. An α1-adrenoceptor subtype corresponding to the cloned α1A/D-adrenoceptor appears to exist in rat kidney. Among cloned α1-adrenoceptor subtypes, the bovine α1C-adrenoceptor bears the closest resemblance to the pharmacologically-defined α1A-adrenoceptor in rat cortex and to one of the chloroethylclonidine-insensitive subtypes in rat kidney. © 1994 Springer-Verlag.