MECHANISM OF THE INHIBITION OF PLATELET-AGGREGATION PRODUCED BY PROSTAGLANDIN-F2-ALPHA
MECHANISM OF THE INHIBITION OF PLATELET-AGGREGATION PRODUCED BY PROSTAGLANDIN-F2-ALPHA
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DOI：
10.1016/0090-6980(85)90083-8
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发表时间：
1985-01-01
影响因子：
2.9
通讯作者：
WILSON, NH
中科院分区：
文献类型：
--
作者：
ARMSTRONG, RA;JONES, RL;WILSON, NH
由PGF 2 α产生的人血小板聚集的抑制[前列腺素F2 α]对血栓素A2模拟物没有特异性。由PAF [血小板活化因子]和凝血酶诱导的聚集波也被PGF 2 α抑制。（8 μ M）; ADP不受影响。这些作用仍然见于阿司匹林治疗的供体的血小板和对血栓素样激动剂脱敏的血小板（例如，11，9-环氧甲烷PGH 2）。血栓素受体拮抗剂EP 045（高达20 μ M）对PAF、凝血酶和ADP诱导的初级聚集没有影响。EP 045（IC 50 [50%抑制] = 0.5 μ M），但不包括PGF 2 α。(28μ M）取代了[3 H] 9，11-环氧亚甲基PGH 2与洗涤的人血小板的特异性结合。PGF2.alpha.产生cAMP水平的小幅增加;这种作用和抗聚集作用都被腺苷酸环化酶抑制剂SQ 22536 [9-（tetrahydro-2-furyl）adenine]减弱。由PGF 2 α诱导的cAMP的升高。ADP的存在比凝血酶、PAF或血栓烷模拟物更大程度地抑制。聚集剂抑制这种增加的能力与它们对PGF 2 α抑制的敏感性成反比。显然，PGF 2 α的作用非常微弱。对cAMP产生的影响足以说明其抑制活性;它不太可能是其他人所建议的血小板血栓烷受体的竞争性拮抗剂。
The inhibition of human platelet aggregation produced by PGF2.alpha. [prostaglandin F2.alpha.] is not specific for thromboxane A2 mimetics. Aggregation waves induced by PAF [platelet-activating factor] and thrombin are also inhibited by PGF2.alpha. (8 .mu.M); ADP is unaffected. These effects are still seen in platelets from aspirin-treated donors and platelets desensitized to thromboxane-like agonists (e.g., 11,9-epoxymethano PGH2). The thromboxane receptor antagonist EP 045 (up to 20 .mu.M) had no effect on primary aggregation induced by PAF, thrombin and ADP. EP 045 (IC50 [50% inhibition] = 0.5 .mu.M), but not PGF2.alpha. (28 .mu.M), displaces the specific binding of [3H] 9,11-epoxymethano PGH2 to washed human platelets was previously shown. PGF2.alpha. produces small increases in cAMP levels; both this effect and the anti-aggregation are diminished by the adenyl cyclase inhibitor SQ 22536 [9-(tetrahydro-2-furyl)adenine]. The rise in cAMP induced by PGF2.alpha. is inhibited to a greater extent by the presence of ADP than by thrombin, PAF or a thromboxane mimetic. The ability of aggregating agents to inhibit this increase correlates inversely with their sensitivity to inhibition by PGF2.alpha.. Apparently, the very weak effect of PGF2.alpha. on cAMP production is sufficient to account for its inhibitory activity; it is unlikely to be a competitive antagonist at the platelet thromboxane receptor as suggested by others.