The activation by Ca2+ of platelet phospholipase A2. Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate.
The activation by Ca2+ of platelet phospholipase A2. Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate.
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Ca2+ 激活血小板磷脂酶 A2。
DOI：
10.1016/0304-4165(78)90296-9
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发表时间：
1978
期刊：
影响因子：
--
通讯作者：
D. Deykin
中科院分区：
文献类型：
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作者：
S. Rittenhouse;S. Rittenhouse;D. Deykin;D. Deykin
通过将血小板与1 mM二丁酰环磷酸腺苷（Bt 2环AMP）或0.6 mM 8-（N，N-二乙氨基）-辛基-3，4，5-三甲氧基苯甲酸酯（TMB-8）（一种细胞内钙拮抗剂）孵育，发现凝血酶诱导的人血小板磷脂酰胆碱中花生四烯酸的释放被削弱了90%以上。花生四烯酸掺入血小板磷脂不增强Bt 2环AMP。凝血酶处理的血小板与Bt 2环AMP或TMB-8孵育的外部Ca 2+的添加不抵消所观察到的抑制。然而，当使用二价阳离子载体A23187作为活化剂时，Bt 2环AMP或TMB-8产生的抑制作用要小得多。加入Ca ~（2+）可克服抑制作用。高浓度的A23187可以克服Bt 2环AMP对花生四烯酸释放的抑制作用，但TMB-8不能。当Mg 2+取代Ca 2+，离子载体诱导的释放花生四烯酸从磷脂酰胆碱的无胆固醇的控制是压抑和抑制Bt 2环AMP略有增强。加入Ca ~（2+）可使血小板裂解液的磷脂酶A_2活性增加，而加入A_23187或Bt_2环腺苷酸对磷脂酶A_2活性无影响。我们认为，Bt 2环AMP可能会促进区室化的Ca 2+，从而抑制磷脂酶A的活性。离子载体可以克服这种区室化。相比之下，TMB-8可以抑制血小板Ca 2+原位储存或以不易被高浓度离子载体逆转的方式限制Ca 2+进入磷脂酶A。
Thrombin-induced release of arachidonic acid from human platelet phosphatidylcholine is found to be more than 90% impaired by incubation of platelets with 1 mM dibutyryl cyclic adenosine monophosphate (Bt2cyclic AMP) or with 0.6 mM 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular calcium antagonist. Incorporation of arachidonic acid into platelet phospholipids is not enhanced by Bt2cyclic AMP. The addition of external Ca2+to thrombin-treated platelets incubated with Bt2cyclic AMP or TMB-8 does not counteract the observed inhibition. However, when divalent cation ionophore A23187 is employed as an activating agent, much less inhibition is produced by Bt2cyclic AMP or TMB-8. The inhibition which does result can be overcome by added Ca2+. Inhibition of arachidonic acid liberation by Bt2cyclic AMP, but not by TMB-8, can be overcome by high concentrations of A23187. When Mg2+is substituted for Ca2+, ionophore-induced release of arachidonic acid from phosphatidylcholine of inhibitor-free controls is depressed and inhibition by Bt2cyclic AMP is slightly enhanced. The phospholipase A2activity of platelet lysates is increased by the presence of added Ca2+, however, the addition of either A23187 or Bt2cyclic AMP is without effect on this activity. We suggest that Bt2cyclic AMP may promote a compartmentalization of Ca2+, thereby inhibiting phospholipase A activity. The compartmentalization may be overcome by ionophore. By contrast, TMB-8 may immobilize platelet Ca2+stores in situ or restrict access of Ca2+to phospholipase A in a manner not susceptible to reversal by high concentrations of ionophore.