Enhancement of ATPase activity by a lipid peroxide of arachidonic acid in rat brain microvessels.
The effects of 15-hydroperoxyarachidonic acid (15-HPAA) on Na+, K+- and Mg+-ATPase activities in the blood-brain barrier (BBB) were examined using rat brain microvessels (MV). 15-HPAA markedly stimulated these ATPase activities in MV at low concentrations whereas the synaptosomal Na+, K+-ATPase activity was inhibited in a dose-dependent manner. Further neurochemical analysis revealed that this stimulatory effect of 15-HPAA in MV was not due to a simple detergent-like action of the compound on the membranes but rather to stimulation of the phospholipase A2 and lipoxygenase activity within MV. In addition, it was shown that free radical reactions were involved in the mechanism. Since such anti-edema drugs as 1,2-bis(nicotinamido)propane were proved to be potent suppressors of the enhanced ATPase activity, further speculations on the role of this effect for ischemic brain edema are offered.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D001929:Brain Edema / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000494:pharmacology; D005609:Free Radicals; D006873:Hydroquinones / Q000494:pharmacology; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology; D014810:Vitamin E / Q000494:pharmacology
D001095:Arachidonic Acids; D005227:Fatty Acids; D005609:Free Radicals; D006873:Hydroquinones; D015289:Leukotrienes; D008054:Lipid Peroxides; D014810:Vitamin E; D009536:Niacinamide; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D008084:Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D011796:Quinacrine; C042625:nicaraven; C031927:hydroquinone