Heterogenous properties of alpha2 adrenoceptors in particulate and soluble preparations of human platelet and rat and rabbit kidney

Abstract

Alpha2 adrenoceptors of the human platelet and rat and rabbit renal cortex were compared in binding studies using the selective antagonist ligand [3H]rauwolscine. Significant differences in the pharmacological characteristics of the alpha2 adrenoceptor were observed between the tissues with reference to both absolute drug affinities as well as rank order of drug potency. Two subsets of the alpha2 adrenoceptor sites could be described: one exhibiting equal affinity for the alpha2 selective diastereoisomers, yohimbine and rauwolscine, and low affinity for the alpha1 antagonist prazosin (human platelet); the other displaying significantly higher affinity for rauwolscine than yohimbine but also relatively high affinity for prazosin (rat and rabbit kidney). Digitonin solubilised alpha2 adrenoceptors from these tissues identified by [3H]rauwolscine generally displayed reduced drug affinities. This was most apparent for agonists (10–50-fold lower) indicating separation of the soluble receptors from the guanine nucleotide binding proteins. However, the solubilised alpha2 adrenoceptors retained the overall pharmacological properties of their respective membrane receptors, including rank order of drug potency, reflecting similar inter-tissue differences. These results suggest that the pharmacological differences in alpha2 adrenoceptors observed are not species specific and are not related to variation in receptor effector coupling mechanisms or problems of ligand access due to membrane constraints. This may reflect true intrinsic differences in the molecular structure of these receptors.