INTERACTION OF SELECTIVE α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS WITH HUMAN AND RABBIT BLOOD PLATELETS

E-ISSN： 1476-5381|71|1|121-134

ISSN： 0007-1188

Source： BRITISH JOURNAL OF PHARMACOLOGY (ELECTRONIC), Vol.71, Iss.1, 1980-01, pp. : 121-134

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Abstract

1The selectivity of α‐adrenoceptors mediating the pro‐aggregatory response of human and rabbit platelets to adrenaline and the conditions required to permit expression of an aggregatory response to partial agonists at these α‐adrenoceptors have been studied.2Yohimbine causes effective blockade of the pro‐aggregatory responses whereas indoramin and prazosin are ineffective.3The clonidine analogue, UK‐14304, is nearly as effective as adrenaline in inducing an aggregatory response in human platelets and a pro‐aggregatory response in rabbit platelets. Cross‐tachyphylaxis between adrenaline and UK‐14304 has been demonstrated.4Clonidine is a weak agonist for the pro‐aggregatory response of rabbit platelets and in some donors for the aggregatory response of human platelets.5Methoxamine induces a pro‐aggregatory response in human platelets which is blocked by indoramin or prazosin but not by yohimbine. No such response to methoxamine is observed in rabbit platelets.6The divalent cation ionophore, A‐23187, induces an aggregatory response to clonidine (in platelets from a non‐responsive donor), phenylephrine and methoxamine in human platelets and to adrenaline, UK‐14304 and clonidine in rabbit platelets. A secretory response to clonidine is also induced by A‐23187 in human platelets.7The adenylate cyclase inhibitor, SQ‐22536, is ineffective in either inducing a response to the α‐agonists or potentiating the effect of A‐23187.8The aggregatory responses to adrenaline and UK‐14304 in rabbit platelets and to clonidine in human and rabbit platelets, which can be induced by A‐23187, are blocked by yohimbine but not by prazosin or indoramin.9From these studies we conclude that the pro‐aggregatory responses of human and rabbit platelets to adrenaline are mediated primarily by α2‐adrenoceptors. The presence of α1‐adrenoceptors on human platelets is confirmed but these receptors do not appear to be present on rabbit platelets. The conditions required for expression of an aggregatory response to partial agonists at the human and rabbit platelet α‐adrenoceptors implicate an increase in cytosolic Ca2+ concentration as a key event in stimulus‐response coupling but do not indicate such a role for depression of cyclic adenosine‐3′,5′‐monophosphate concentration.