FUNCTIONAL EVIDENCE FOR HETEROGENEITY OF PERIPHERAL PREJUNCTIONAL ALPHA-2-ADRENOCEPTORS

1. We have examined the potencies of a series of α2-adrenoceptor antagonists in functional studies of prejunctional α2-adrenoceptors in rat atrium and vas deferens, and compared potencies with affinities for the (α2A)-ligand binding site of human platelet and the (α2B)-site of rat kidney. 2. Antagonist potency in rat atrium was expressed as an EC30 (concentration producing 30% increase in the stimulation-evoked overflow of tritium in tissues pre-incubated with [3H]-noradrenaline). Antagonist potency in rat vas deferens was expressed as a pA2 or K(B) at antagonizing the inhibition by the α2-adrenoceptor agonist xylazine of the isometric twitch to a single stimulus, or as an EC30. 3. In ligand binding studies, K(i) values were obtained for the displacement by α-adrenoceptor antagonists of [3H]-yohimbine binding to human platelet or rat kidney membranes. 4. In functional studies, three antagonists (ARC 239, prazosin and chlorpromazine) distinguished between prejunctional α2-adrenoceptors of rat atrium (EC30) and rat vas deferens (pA2) and showed 49, 12 and 7 times higher potency in rat atrium, respectively. ARC 239 was also 17 times more potent in rat atrium than rat vas deferens when EC30 values were compared. 5. The correlation of affinity for the (α2A)-site of human platelet was better with prejunctional potency in rat vas deferens than rat atrium. 6. The correlation of affinity for the (α2B)-site of rat kidney was better with prejunctional potency in rat atrium than rat vas deferens. 7. It is concluded that prejunctional α2-adrenoceptors of rat vas deferens and rat atrium differ, and these receptors may resemble the (α2A)- and (α2B)-ligand binding sites, respectively.