Novel α₂-adrenoreceptors primarily responsible for inducing human platelet aggregation

Abstract

BLOOD PLATELETS isolated from humans, in contrast to those from other mammalian species, aggregate on exposure to adrenaline or noradrenaline¹. Studies using α antagonists have shown that this effect results from occupancy of an α adrenoreceptor^2,3. However, Jakobs has reported that selective α agonists such as clonidine and phenylephrine bind with high affinity to the platelet α adrenoreceptor^4,5, but fail either to induce an aggregation response⁶ or to inhibit platelet adenylate cyclase⁶, in contrast to the effects of natural agonists such as adrenaline^1,7. Instead, such α agonists seem to act as antagonists at the platelet adrenoreceptor⁶. α Adrenoreceptors in other tissues have been classified as α₁ (postsynaptic) or α₂ (presynaptic) on the basis of their affinities for various selective α agonists and antagonists⁸. Jakobs⁶ has, however, interpreted his data on the human platelet adrenoreceptor as indicating the existence of a third category of α adrenoreceptor at which only the natural catecholamines are agonists. We report here that we have confirmed the observation that clonidine and phenylephrine are ineffective in inducing aggregation of human platelets and act as inhibitors of the response to adrenaline. However, further examination has revealed that the effects of these selective α agonists differ in certain important respects from those of selective α antagonists, thus requiring substantial modification of the thesis advanced by Jakobs⁶.