Mikashima H, Nakao T, Goto K, Ochi H, Yasuda H, Tsumagari T
Thromb Res. 1984 Sep 1;35(5):589-94. doi: 10.1016/0049-3848(84)90291-3.
The effects of 6-(2, 3, 4, 5-tetrahydro-5-methyl-3-oxo-pyridazine-6-yl)-1, 2, 3, 4-tetrahydro -1-methyl quinolin-2-one (Y-590) on platelet phosphodiesterases (PDE) were investigated. Y-590 incubated with washed rabbit platelets did not affect the cyclic AMP (cAMP) content. But when added to the washed platelets 1.5 minutes before prostaglandin I2 (PGI2), it potentiated the ability of the latter to increase cAMP. Y-590 potently inhibited cAMP-PDE in rabbit platelets, but its inhibitory effect on cGMP-PDE was less potent. Its G/A (IC50 for cGMP-PDE/IC50 for cAMP-PDE) was 1055, about 60 times that of papaverine. The concentration of Y-590 causing inhibition of cAMP-PDE was the same degree as that inhibiting platelet aggregation. These results indicate that Y-590 is a selective inhibitor of cAMP-PDE which exerts its anti-platelet activity by inhibiting cAMP degradation in platelets.
研究了6-(2,3,4,5-四氢-5-甲基-3-氧代哒嗪-6-基)-1,2,3,4-四氢-1-甲基喹啉-2-酮(Y-590)对血小板磷酸二酯酶(PDE)的影响。Y-590与洗涤过的兔血小板孵育不影响环磷酸腺苷(cAMP)含量。但在前列腺素I2(PGI2)加入前1.5分钟添加到洗涤过的血小板中时，它增强了后者增加cAMP的能力。Y-590能有效抑制兔血小板中的cAMP-PDE，但其对cGMP-PDE的抑制作用较弱。其G/A(cGMP-PDE的IC50/cAMP-PDE的IC50)为1055，约为罂粟碱的60倍。引起cAMP-PDE抑制的Y-590浓度与抑制血小板聚集的浓度相同。这些结果表明，Y-590是一种cAMP-PDE的选择性抑制剂，通过抑制血小板中cAMP的降解发挥其抗血小板活性。
