Abstract
The recombinant α2-adrenoceptors, designated as α2a and α2d, 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 α2a- (human, pig) or α2d- (rat, mouse, guinea pig, cow) adrenoceptor. Radioligand binding assays in rabbit adipocyte suggest α2D-adrenoceptor pharmacology. However, functional studies examining prejunctional α2-adrenoceptors in several tissues pharmacologically define the receptor of the rabbit as an α2A-adrenoceptor rather than an α2D-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 α2a-adrenoceptor or the rat α2d-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 α2a-adrenoceptor (r2 = 0.68–0.77) than with the α2d-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 α2A-adrenoceptor pharmacology. Subtle differences in the α2-adrenoceptor binding characteristics of these native rabbit tissues compared with the recombinant human α2a-adrenoceptor may result either from minor differences in the sequence of human and rabbit α2a-adrenoceptors or from differences in the environment to which native and recombinant receptors are exposed.
Footnotes
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↵1 Current address: Wyeth-Ayerst Research, P.O. Box 42528, Philadelphia, PA 19101.
- Abbreviations:
- RX 821002
- 2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline
- WB 4101
- 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane
- BAM 1303
- 1-(2-bromo-6-methylergolin-8b-ylmethyl)-2-phenylimidazole
- ARC 239
- 2-(4-(2-methoxyphenyl)-piperazine-1-yl)ethyl-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione
- SK&F 104078
- 6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-1,2,3,4-tetrahydro-1H-3-benzazepine
- Received December 27, 2000.
- Accepted March 18, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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