Lasserre B, Pham Huu Chanh A, Palhares de Miranda A L, Tronche P, Couquelet J, Rubat C
C.N.R.S. Institut de Physiologie, Toulouse, France.
Prostaglandins Leukot Essent Fatty Acids. 1988 Aug;33(2):143-7. doi: 10.1016/0952-3278(88)90154-8.
The effects of 2-(2 dimethylaminoethyl) 5-benzylidene 6-methyl (2H,4H)-3-pyridazinone (III) were studied on the biosynthesis of TXA2 and PGI2 in vitro the TXA2 and PGI2 synthetase activity of heart tissue. Biosyntheses of TXA2 and PGI2 were carried out using arachidonic acid as a substrate and horse platelet and aorta microsomes as sources of TXA2 and PGI2 synthetases respectively. TXB2 and 6-keto PGF1 alpha were determined by RIA. III--did not significantly modify either the biosynthesis of PGI2 in vitro or the PGI2 synthetase activity of heart tissue. did not significantly inhibit TXA2 biosynthesis in vitro but markedly reduced the TXA2 synthetase activity of heart tissue: for a microsomal fraction concentration of 100 micrograms protein, the ID50 was 6.37 X 10(-5) M +/- 1.29 X 10(-8) M. Thus III behaves as a specific inhibitor of the TXA2 synthetase activity of heart tissue and could have a beneficial use in therapeutics.
研究了2-(2-二甲基氨基乙基)-5-亚苄基-6-甲基(2H,4H)-3-哒嗪酮(III)对体外血栓素A2（TXA2）和前列环素（PGI2）生物合成以及心脏组织中TXA2和PGI2合成酶活性的影响。以花生四烯酸为底物，分别以马血小板和主动脉微粒体作为TXA2和PGI2合成酶的来源进行TXA2和PGI2的生物合成。采用放射免疫分析法测定血栓素B2（TXB2）和6-酮-前列腺素F1α（6-keto PGF1α）。III在体外对PGI2的生物合成或心脏组织的PGI2合成酶活性均无显著影响。在体外对TXA2生物合成无显著抑制作用，但显著降低了心脏组织的TXA2合成酶活性：对于微粒体部分浓度为100微克蛋白质，半数抑制浓度（ID50）为6.37×10⁻⁵M±1.29×10⁻⁸M。因此，III表现为心脏组织TXA2合成酶活性的特异性抑制剂，在治疗方面可能具有有益用途。
