Abstract

The recombinant α₂-adrenoceptors, designated as α_2a and α_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 α₂-adrenoceptors of a given species have pharmacological characteristics corresponding to either the α_2a- (human, pig) or α_2d- (rat, mouse, guinea pig, cow) adrenoceptor. Radioligand binding assays in rabbit adipocyte suggest α_2D-adrenoceptor pharmacology. However, functional studies examining prejunctional α₂-adrenoceptors in several tissues pharmacologically define the receptor of the rabbit as an α_2A-adrenoceptor rather than an α_2D-adrenoceptor. We characterized the α₂-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 α_2a-adrenoceptor or the rat α_2d-adrenoceptor. Pharmacological characteristics of the adipocyte and platelet receptor were very similar, with an excellent correlation between pK_i values (r² = 0.95, slope of regression = 1.01). Drug affinities for both platelet and adipocyte receptors correlated better with the α_2a-adrenoceptor (r² = 0.68–0.77) than with the α_2d-adrenoceptor (r² = 0.37–0.38). Despite the relatively low affinity of the rabbit adipocyte α₂-adrenoceptor for yohimbine and rauwolscine, this receptor, as well as the platelet receptor, have α_2A-adrenoceptor pharmacology. Subtle differences in the α₂-adrenoceptor binding characteristics of these native rabbit tissues compared with the recombinant human α_2a-adrenoceptor may result either from minor differences in the sequence of human and rabbit α_2a-adrenoceptors or from differences in the environment to which native and recombinant receptors are exposed.