Rabbit alpha(2)-adrenoceptors: Both platelets and adipocytes have alpha(2A)-pharmacology

The recombinant alpha (2)-adrenoceptors, designated as alpha (2a) and alpha (2d), have highly similar amino acid sequences, but distinct pharmacologic al properties. It has been suggested that these two receptor subtypes are s pecies orthologs, since the alpha (2)-adrenoceptors of a given species have pharmacological characteristics corresponding to either the alpha (2a)- (h uman, pig) or alpha (2d)- (rat, mouse, guinea pig, cow) adrenoceptor. Radio ligand binding assays in rabbit adipocyte suggest alpha (2D)-adrenoceptor p harmacology. However, functional studies examining prejunctional alpha (2)- adrenoceptors in several tissues pharmacologically define the receptor of t he rabbit as an alpha (2A)-adrenoceptor rather than an alpha (2D)-adrenocep tor. We characterized the alpha (2)-adrenoceptor of rabbit adipocyte and pl atelet, comparing the ability of norepinephrine and 13 adrenoceptor antagon ists to inhibit the binding of [H-3]RX821002 with the affinity of these dru gs for the human alpha (2a)-adrenoceptor or the rat alpha (2d)-adrenoceptor . Pharmacological characteristics of the adipocyte and platelet receptor we re very similar, with an excellent correlation between pK(i) values (r(2) = 0.95, slope of regression = 1.01). Drug affinities for both platelet and a dipocyte receptors correlated better with the alpha (2a)-adrenoceptor (r(2) = 0.68-0.77) than with the alpha (2d)-adrenoceptor (r(2) = 0.37-0.38). Des pite the relatively low affinity of the rabbit adipocyte alpha (2)-adrenoce ptor 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 t issues compared with the recombinant human alpha (2a)-adrenoceptor may resu lt either from minor differences in the sequence of human and rabbit alpha (2a)-adrenoceptors or from differences in the environment to which native a nd recombinant receptors are exposed.