Bosin T R, Schaltenbrand S L
Pharmacology Section, Indiana University School of Medicine, Bloomington 47405.
Biochem Pharmacol. 1991;41(6-7):967-74. doi: 10.1016/0006-2952(91)90203-h.
The effect of oxidant stress produced by redox cycling of substituted 1,4-naphthoquinones on the activity of platelet (Na(+)-K+)ATPase and the active transport of serotonin (5-HT) was studied. 2-Methyl-1,4-naphthoquinone (menadione) produced a concentration-dependent (0-100 microM) and time-dependent (2-20 min) stimulation of platelet 5-HT transport. Exogenous superoxide dismutase (250 units) and/or catalase (500 units) failed to block the stimulation. Fluoxetine, an inhibitor of the platelet 5-HT transporter, blocked menadione-induced stimulation of 5-HT uptake as did ouabain, an inhibitor of platelet (Na(+)-K+)ATPase. The structure-activity relationship of select 1,4-naphthoquinones suggested that stimulation was due to redox cycling and not arylation. The kinetics of 5-HT transport revealed that menadione markedly increased the maximal rate of 5-HT transport (Vmax control = 20.6 +/- 2.0 pmol/10(8) platelets/4 min vs Vmax menadione = 46.4 +/- 3.9 pmol/10(8) platelets/4 min) but did not significantly alter the Km values. The activity of (Na(+)-K+)ATPase was determined by measuring the uptake of 86Rb+ into intact platelets. Menadione produced a concentration-dependent and time-dependent stimulation of platelet 86Rb+ uptake. These changes in platelet (Na(+)-K+)ATPase activity paralleled the changes observed in 5-HT transport and were inhibited in a concentration-dependent manner by ouabain. The data have shown that the redox cycling of 1,4-naphthoquinones caused an increase in (Na(+)-K+)ATPase activity that resulted in the stimulation of the rate of platelet 5-HT transport.
研究了取代的1,4 - 萘醌的氧化还原循环所产生的氧化应激对血小板（Na(+)-K+)ATP酶活性及5 - 羟色胺（5 - HT）主动转运的影响。2 - 甲基 - 1,4 - 萘醌（甲萘醌）对血小板5 - HT转运产生浓度依赖性（0 - 100 microM）和时间依赖性（2 - 20分钟）的刺激作用。外源性超氧化物歧化酶（250单位）和/或过氧化氢酶（500单位）未能阻断这种刺激。血小板5 - HT转运体抑制剂氟西汀以及血小板（Na(+)-K+)ATP酶抑制剂哇巴因均能阻断甲萘醌诱导的5 - HT摄取刺激。所选1,4 - 萘醌的构效关系表明，刺激是由于氧化还原循环而非芳基化作用。5 - HT转运的动力学研究显示，甲萘醌显著提高了5 - HT转运的最大速率（对照组Vmax = 20.6 ± 2.0 pmol/10(8)个血小板/4分钟，甲萘醌组Vmax = 46.4 ± 3.9 pmol/10(8)个血小板/4分钟），但并未显著改变Km值。通过测量86Rb+进入完整血小板的摄取量来测定（Na(+)-K+)ATP酶的活性。甲萘醌对血小板86Rb+摄取产生浓度依赖性和时间依赖性的刺激作用。血小板（Na(+)-K+)ATP酶活性的这些变化与5 - HT转运中观察到的变化平行，并且被哇巴因以浓度依赖性方式抑制。数据表明，1,4 - 萘醌的氧化还原循环导致（Na(+)-K+)ATP酶活性增加，进而刺激了血小板5 - HT转运速率。
