[A study on the protective mechanism of phenytoin in transient global ischemia].
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.
Kurosawa
K
K
Institute of Brain Diseases, Tohoku University School of Medicine, Sendai, Japan.
Imaizumi
S
S
Kinouchi
H
H
Yoshimoto
T
T
Suzuki
J
J
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002121:Calcium Channel Blockers; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000227:Adenine Nucleotides; D002121:Calcium Channel Blockers; D005230:Fatty Acids, Nonesterified; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D010672:Phenytoin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium