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Vol. 298, Issue 1, 219-225, July 2001

Rabbit alpha 2-Adrenoceptors: Both Platelets and Adipocytes Have alpha 2A-Pharmacology

Diane P. Naselsky, Daryl Ashton, Robert R. Ruffolo, Jr.1 and J. Paul Hieble

Department of Pharmacology, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania

The recombinant alpha 2-adrenoceptors, designated as alpha 2a and alpha 2d, have highly similar amino acid sequences, but distinct pharmacological properties. It has been suggested that these two receptor subtypes are species orthologs, since the alpha 2-adrenoceptors of a given species have pharmacological characteristics corresponding to either the alpha 2a- (human, pig) or alpha 2d- (rat, mouse, guinea pig, cow) adrenoceptor. Radioligand binding assays in rabbit adipocyte suggest alpha 2D-adrenoceptor pharmacology. However, functional studies examining prejunctional alpha 2-adrenoceptors in several tissues pharmacologically define the receptor of the rabbit as an alpha 2A-adrenoceptor rather than an alpha 2D-adrenoceptor. We characterized the alpha 2-adrenoceptor of rabbit adipocyte and platelet, comparing the ability of norepinephrine and 13 adrenoceptor antagonists to inhibit the binding of [3H]RX821002 with the affinity of these drugs for the human alpha 2a-adrenoceptor or the rat alpha 2d-adrenoceptor. Pharmacological characteristics of the adipocyte and platelet receptor were very similar, with an excellent correlation between pKi values (r2 = 0.95, slope of regression = 1.01). Drug affinities for both platelet and adipocyte receptors correlated better with the alpha 2a-adrenoceptor (r2 = 0.68-0.77) than with the alpha 2d-adrenoceptor (r2 = 0.37-0.38). Despite the relatively low affinity of the rabbit adipocyte alpha 2-adrenoceptor for yohimbine and rauwolscine, this receptor, as well as the platelet receptor, have alpha 2A-adrenoceptor pharmacology. Subtle differences in the alpha 2-adrenoceptor binding characteristics of these native rabbit tissues compared with the recombinant human alpha 2a-adrenoceptor may result either from minor differences in the sequence of human and rabbit alpha 2a-adrenoceptors or from differences in the environment to which native and recombinant receptors are exposed.

1 Current address: Wyeth-Ayerst Research, P.O. Box 42528, Philadelphia, PA 19101.

0022-3565/01/2981-0219$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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