Mammalian platelet adrenoceptors.

Abstract

Mammalian platelets vary widely in their responses to catecholamines in part because these agonists can act via excitatory alpha- and inhibitory beta-adrenoceptors. In the absence of antagonists, adrenaline enhances the response of rabbit platelets to an excitatory agonist, e.g. adenosine-5'-O-(1-thiodiphosphate) (ADP-alpha-s) acting at another receptor, but has no effect on the response of rat or guinea pig platelets to such an agonist. In the presence of a beta-adrenoceptor antagonist, adrenaline enhances the response of rat, but not guinea-pig platelets to ADP-alpha-S and the extent of the enhanced effect on rabbit platelets is increased. In the presence of an alpha-adrenoceptor antagonist, adrenaline inhibits the response of rabbit and rat platelets to ADP-alpha-S but has no such effect on the response of guinea-pig platelets. Studies using selective agonists and antagonists demonstrate that the excitatory response of rat platelets to adrenaline is mediated by an alpha 2-adrenoceptor, and the inhibitory response of rabbit platelets to adrenaline by a beta 2-adrenoceptor as is the case in other species which have been examined. The mean alpha 2-adrenoceptor density on human, rabbit, rat and guinea-pig platelets as assessed using [3H]-yohimbine as radioligand is obtained as 258, 270, 42 and less than 10 receptors per platelet. The mean beta 2-adrenoceptor density on human, rabbit, rat and guinea-pig platelets as assessed using (-)-[125I]-iodocyanopindolol is obtained as 66, 14, 41 and less than 5 receptors per platelet. The nature of the effect of adrenaline on the response of mammalian platelets to other excitatory agonists, e.g. ADP-alpha-S, appears therefore to be largely determined by the absolute number of alpha 2-adrenoceptors and by the relative content of alpha 2- and beta 2-adrenoceptors on these cells for the species which have been examined in this analysis.