Saareks V, Mucha I, Sievi E, Riutta A
Department of Pharmacological Sciences, University of Tampere, Finland.
Pharmacol Toxicol. 1999 Jun;84(6):274-80. doi: 10.1111/j.1600-0773.1999.tb01494.x.
The in vitro effects of nicotinic acid (10-1000 microM), pyridoxine (0.1-500 microM) and pyridoxal-5'-phosphate (0.1-500 microM) and the ex vivo effects of nicotinic acid (2500 mg orally during 12 h) and pyridoxine (600 mg orally daily for seven days) on arachidonic acid metabolism were investigated in calcium ionophore A23187 (calcimycin)-stimulated human whole blood. In vitro nicotinic acid stimulated prostaglandin E2, thromboxane B2 and leukotriene E4 synthesis. Pyridoxine at all concentrations and pyridoxal-5'-phosphate at the highest concentration stimulated prostaglandin E2 and thromboxane B2 production, but had no effect on leukotriene E4 synthesis. Nicotinic acid treatment increased ex vivo prostaglandin E2, thromboxane B2 and leukotriene E4 synthesis to 185%, 165% and 175% of the initial values, respectively. In the pyridoxine-treated subjects, ex vivo prostaglandin E2, thromboxane B2 and leukotriene E4 synthesis was decreased after seven days to 75%, 65% and 45% of the initial values, respectively. In the present study the effects of nicotinic acid on the 5-lipoxygenase pathway in arachidonic acid metabolism were studied for the first time and the drug was found to stimulate this pathway in vitro and ex vivo. In vitro pyridoxine and pyridoxal-5'-phosphate had no effect on the 5-lipoxygenase pathway. The inhibition of leukotriene synthesis by pyridoxine ex vivo might be of therapeutic importance.
研究了烟酸（10 - 1000微摩尔）、吡哆醇（0.1 - 500微摩尔）和磷酸吡哆醛（0.1 - 500微摩尔）的体外效应，以及烟酸（12小时内口服2500毫克）和吡哆醇（每日口服600毫克，共七天）对钙离子载体A23187（钙霉素）刺激的人全血中花生四烯酸代谢的体内效应。体外实验中，烟酸刺激了前列腺素E2、血栓素B2和白三烯E4的合成。所有浓度的吡哆醇和最高浓度的磷酸吡哆醛刺激了前列腺素E2和血栓素B2的产生，但对白三烯E4的合成没有影响。烟酸处理使体内前列腺素E2、血栓素B2和白三烯E4的合成分别增加到初始值的185%、165%和175%。在接受吡哆醇治疗的受试者中。七天后，体内前列腺素E2、血栓素B2和白三烯E4的合成分别降至初始值的75%、65%和45%。在本研究中，首次研究了烟酸对花生四烯酸代谢中5 - 脂氧合酶途径的影响，发现该药物在体外和体内均能刺激该途径。体外实验中，吡哆醇和磷酸吡哆醛对5 - 脂氧合酶途径没有影响。吡哆醇在体内对白三烯合成的抑制可能具有治疗意义。
