Ally A, Buist R, Mills P, Reuhl K
Biomedical NMR, National Research Council of Canada, Ottawa, Ontario.
Pharmacol Biochem Behav. 1993 Mar;44(3):555-63. doi: 10.1016/0091-3057(93)90166-q.
The effects of two organometals on heart, platelet, and aorta prostaglandin biosynthesis were examined in vitro. Methylmercuric chloride (MMC, 39-796 nM) increased the biosynthesis of thromboxane A2 (TxA2) and prostacyclin (PGI2) in the heart and stimulated the biosynthesis of PGI2 in incubates of aorta rings. The aorta biosynthesis of PGI2 was monitored by its inhibition of platelet aggregation and serotonin [5-hydroxytryptamine (5-HT)] secretion, while the metabolites 6-keto-PGF1a and TxB2 were quantified by radioimmunoassay. In platelet experiments, low concentrations of MMC (5 microM) enhanced aggregation to adenosine diphosphate (ADP) and at high concentrations MMC (50-100 microM) directly stimulated aggregation and 5-HT secretion. These effects of MMC were inhibited by nonsteroidal antiinflammatory drug, thromboxane synthetase, and phospholipase A2 inhibitors. Trimethyltin (TMT), another highly toxic organometal, had no effect on prostaglandin biosynthesis in either heart or aorta incubates. TMT did not increase platelet aggregation responses to ADP, nor did it directly trigger aggregation. At moderate concentrations, TMT (20-45 microM) slightly depressed ADP aggregation; however, this was paradoxically associated with increased 5-HT secretion. In platelets pretreated with either NDGA or ASA, TMT in the absence of aggregation enhanced 5-HT secretion in response to ADP. TMT, unlike MMC, did not stimulate platelet TxB2 biosynthesis from exogenous [3H]arachidonic acid, whereas MMC stimulates heart, vascular, and platelet eicosanoid biosynthesis. TMT, unlike MMC, does not directly activate the arachidonic acid cascade.
体外研究了两种有机金属对心脏、血小板和主动脉前列腺素生物合成的影响。氯化甲基汞（MMC，39 - 796 nM）增加了心脏中血栓素A2（TxA2）和前列环素（PGI2）的生物合成，并刺激了主动脉环孵育物中PGI2的生物合成。通过其对血小板聚集和血清素[5 - 羟色胺（5 - HT）]分泌的抑制来监测主动脉中PGI2的生物合成，而代谢产物6 - 酮 - PGF1α和TxB2则通过放射免疫测定法定量。在血小板实验中，低浓度的MMC（5 microM）增强了对二磷酸腺苷（ADP）的聚集，而高浓度的MMC（50 - 100 microM）直接刺激聚集和5 - HT分泌。MMC的这些作用被非甾体抗炎药、血栓素合成酶和磷脂酶A2抑制剂所抑制。三甲基锡（TMT），另一种剧毒有机金属，对心脏或主动脉孵育物中的前列腺素生物合成没有影响。TMT不会增加血小板对ADP的聚集反应，也不会直接引发聚集。在中等浓度下，TMT（20 - 45 microM）略微抑制ADP聚集；然而，这与5 - HT分泌增加自相矛盾。在用去甲二氢愈创木酸（NDGA）或阿司匹林（ASA）预处理的血小板中，在无聚集的情况下TMT增强了对ADP的5 - HT分泌。与MMC不同，TMT不会从外源性[3H]花生四烯酸刺激血小板TxB2生物合成，而MMC会刺激心脏、血管和血小板类花生酸生物合成。与MMC不同，TMT不会直接激活花生四烯酸级联反应。
