The effects of mepacrine and p-bromophenacyl bromide on arachidonic acid release in human platelets.
The effects of mepacrine and p-bromophenacyl bromide on arachidonic acid release in human platelets.
复制标题
Mepacrine 和 p-bromophenacyl bromide 对人血小板中花生四烯酸释放的影响。
DOI：
10.1016/0003-9861(82)90300-9
复制
发表时间：
1982
影响因子：
3.9
通讯作者：
Majerus,PW
中科院分区：
文献类型：
--
作者：
Hofmann,SL;Prescott,SM;Majerus,PW
研究了凝血酶刺激的花生四烯酸释放的两种抑制剂--对溴苯乙酰和美帕克林对磷脂酶C-二甘油酯脂肪酶途径的抑制作用。该途径包括将磷脂酰肌醇水解为二甘油三酯，然后从二甘油酯中释放花生四烯酸，并已被建议作为磷脂酶A2的替代或补充作为花生四烯酸释放的机制。对溴苯基溴，一种有效的烷基化试剂，被证明引起对粗制血小板提取物中磷脂酰肌醇特异性磷脂酶C活性的时间依赖性的抑制；在100μMP-溴苯酰基作用15分钟后，抑制率为90%。然而，在类似的条件下，对溴苯酰溴也被证明可以破坏整个血小板中约一半的可滴定巯基。我们发现凝血酶刺激的5-羟色胺的释放也被抑制花生四烯酸释放的条件所抑制，并且更高水平的对溴苯酰溴降低了双甘酯脂肪酶的活性，进一步证明了对溴苯酰溴的缺乏特异性。甲帕克林对磷脂酰肌醇特异性磷脂酶C的活性有抑制作用，且在低底物浓度时抑制作用更强。内源性磷脂酰肌醇和磷脂酰胆碱对[14C]花生四烯酸的损失也受到抑制。美帕克林也可抑制凝血酶刺激的5-羟色胺释放，但其浓度仅为防止花生四烯酸释放所需浓度的10倍。因此，我们已经证明，这两种抑制花生四烯酸释放的药物是磷脂酰肌醇特异性磷脂酶C-二甘油酯脂肪酶途径的抑制剂。这两种化合物产生的多重效应限制了它们作为试剂来研究花生四烯酸释放的来源和机制。
Two inhibitors of thrombin-stimulated arachidonic acid release from platelets,p-bromophenacyl bromide and mepacrine, were examined for their ability to inhibit the phospholipase C-diglyceride lipase pathway. This pathway involves hydrolysis of phosphatidylinositol to diglyceride, followed by release of arachidonate from diglyceride, and has been proposed as an alternative or addition to phospholipase A2as a mechanism for arachidonate release.p-Bromophenacyl bromide, a potent alkylating agent, was shown to cause a time-dependent inhibition of phosphatidylinositol-specific phospholipase C activity in crude platelet extracts; the inhibition was >90% after 15 min incubation with 100 μmp-bromophenacyl bromide. However,p-bromophenacyl bromide was also shown to destroy about one-half of the titratable sulfhydryl groups in whole platelets under similar conditions. The lack of specificity ofp-bromophenacyl bromide was further demonstrated by our finding that thrombin-stimulated serotonin release was also inhibited by conditions inhibiting arachidonate release and that diglyceride lipase activity was decreased by higher levels ofp-bromophenacyl bromide. Mepacrine was found to inhibit the activity of phosphatidylinositol-specific phospholipase C and had a greater effect at low substrate concentrations. The loss of [14C]arachidonate from both endogenous phosphatidylinositol and phosphatidylcholine in intact platelets was also inhibited. Thrombin-stimulated serotonin release was impaired by mepacrine also but only at a concentration 10-fold greater than that required to prevent arachidonate release. Thus we have shown that these two agents which inhibit arachidonate release are inhibitors of the phosphatidylinositol-specific phospholipase C-diglyceride lipase pathway. The multiple effects produced by both compounds limit their utility as agents to examine the source and mechanism of arachidonate release.
登录
查看更多内容
分离的灌注器官释放花生四烯酸的激素刺激。
DOI：
10.1016/0090-6980(77)90302-1
发表时间：
1977
期刊：
Prostaglandins
影响因子：
--
作者：
P. Isakson;A. Raz;S. Denny;A. Wyche;P. Needleman
通讯作者：
P. Needleman
血小板胞质中磷脂酰肌醇磷酸二酯酶（磷脂酶 C）的表征和特性
影响因子：
3.5
作者：
G. Mauco;H. Chap;L. Douste‐Blazy
通讯作者：
L. Douste‐Blazy
猪甲状腺质膜中偏甘油酯特异性脂肪酶的论证和表征。
DOI：
10.1016/0006-291x(80)90330-7
发表时间：
1980
影响因子：
3.1
作者：
Y. Igarashi;Y. Kondo
通讯作者：
Y. Kondo
Mepacrine 选择性抑制缓激肽给药引起的“兔主动脉收缩物质”的释放
影响因子：
3.3
作者：
B. Vargaftig;N. D. Hai
通讯作者：
N. D. Hai
磷脂酶 A2 活性位点的组氨酸。
影响因子：
2.9
作者：
J. Volwerk;W. A. Pieterson;G. H. D. Haas
通讯作者：
G. H. D. Haas