Stump D C, Macfarlane D E
J Lab Clin Med. 1983 Nov;102(5):779-87.
Human blood platelets display alpha2-adrenergic receptors, which promote platelet aggregation and inhibit the adenylate cyclase. We investigated the effects of the antihypertensive agent clonidine and its analogue para-aminoclonidine on this receptor in the intact human platelet to determine their pharmacological effects and their ability to bind to the receptor by radioligand displacement. Both agents potentiated platelet aggregation induced by a submaximal concentration of ADP. Epinephrine-induced aggregation, on the other hand, was antagonized by clonidine and para-aminoclonidine in a dose-dependent fashion. Both agents inhibited the accumulation of cyclic AMP in platelets exposed to prostaglandin E1 and a phosphodiesterase inhibitor, but to a lesser extent than the inhibition caused by epinephrine. Both antagonized this excess inhibitory action of epinephrine. Clonidine and para-aminoclonidine blocked the binding of [3H]yohimbine (a selective alpha 2-adrenergic antagonist) to intact platelets with half-maximal effects at 0.3 and 0.7 microM, respectively. No evidence for the existence of a second class of binding sites with high affinity for clonidine was seen in intact platelets, either by this technique or by direct binding of [3H]clonidine. It is concluded that these two agents are partial agonists for the alpha 2-adrenergic receptors on blood platelets and that this receptor exists predominantly in the low-affinity state in the intact cell.
人类血小板表达α2 - 肾上腺素能受体，该受体可促进血小板聚集并抑制腺苷酸环化酶。我们研究了抗高血压药物可乐定及其类似物对氨基可乐定在完整人类血小板中对该受体的作用，以确定它们的药理作用以及通过放射性配体置换与受体结合的能力。两种药物均增强了由次最大浓度ADP诱导的血小板聚集。另一方面，可乐定和对氨基可乐定以剂量依赖性方式拮抗肾上腺素诱导的聚集。两种药物均抑制暴露于前列腺素E1和磷酸二酯酶抑制剂的血小板中环磷酸腺苷的积累，但程度小于肾上腺素引起的抑制。两者均拮抗肾上腺素这种过度的抑制作用。可乐定和对氨基可乐定阻断了[3H]育亨宾（一种选择性α2 - 肾上腺素能拮抗剂）与完整血小板的结合，半最大效应浓度分别为0.3和0.7 microM。通过该技术或[3H]可乐定的直接结合，在完整血小板中均未发现对可乐定具有高亲和力的第二类结合位点存在的证据。结论是这两种药物是血小板上α
