Kurosawa K, Imaizumi S, Kinouchi H, Yoshimoto T, Suzuki J
Institute of Brain Diseases, Tohoku University School of Medicine, Sendai, Japan.
No Shinkei Geka. 1989 May;17(5):427-34.
Ischemia gives rise to severe energy depletion and imbalance of Ca2+ homeostasis. This condition leads to activation of phospholipases A2, A1 and to attenuation of ATP dependent reacylation. As a result, free fatty acid (FFA) especially arachidonic acid accumulates. Phenytoin has been reported to blockade the various Ca2+ channels. In this study, we could investigate the effect of phenytoin on the liberation of FFA, energy metabolites, various nucleotides metabolism, Na+, K+-ATPase activity, and water and electrolyte contents in the ischemic brain. Inhibitory effects of phenytoin against FFA accumulation in the ischemia, and increase of parietal cortex water content in the recirculation were brought about. In addition, Na+,K+-ATPase activity in the ischemia was accelerated by phenytoin. Phenytoin may reduce intracellular Ca2+ by blocking the Ca2+ channel into the cytoplasma, or by activation of Na+-Ca2+ exchange transport system following the acceleration of Na+,K+-ATPase activity. Another conceivable way for this acceleration of Na+,K+-ATPase may be derived from the preservation of the energy state, protein metabolism, and lipid metabolism.
缺血会导致严重的能量消耗和钙离子稳态失衡。这种情况会导致磷脂酶A2、A1的激活以及ATP依赖性再酰化作用的减弱。结果，游离脂肪酸（FFA）尤其是花生四烯酸会积累。据报道，苯妥英可阻断各种钙离子通道。在本研究中，我们能够研究苯妥英对缺血性脑内游离脂肪酸释放、能量代谢产物、各种核苷酸代谢、钠钾ATP酶活性以及水和电解质含量的影响。苯妥英对缺血时游离脂肪酸积累具有抑制作用，并能减轻再灌注时顶叶皮质含水量的增加。此外，苯妥英可加速缺血时钠钾ATP酶的活性。苯妥英可能通过阻断钙离子进入细胞质的通道，或在钠钾ATP酶活性加速后激活钠钙交换转运系统来降低细胞内钙离子浓度。钠钾ATP酶活性加速的另一种可能途径可能源于能量状态、蛋白质代谢和脂质代谢的维持。
