Platelet-activating factor antagonist BN52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock.
We have investigated the effects of the specific platelet-activating factor (PAF; 1-alkyl-2-acetyl-glycerophosphocholine) antagonist BN52021 on free fatty acid (FFA) and diacylglycerol (DG) accumulation and on the loss of fatty acids from phosphatidylinositol-4,5-bisphosphate (PIP2) in mouse brain. Mice were pretreated with BN52021 (10 mg/kg, i.p.) 30 min before electroconvulsive shock (ECS) or postdecapitation ischemia. These procedures cause rapid breakdown of PIP2 and accumulation of FFA and DG. Lipid extracts were prepared from microwave-fixed cerebrum and fractionated by TLC, and the fatty acid methyl esters were prepared by methanolysis and quantified by capillary GLC. In saline or vehicle (dimethyl sulfoxide)-treated mice, ECS caused marked accumulation of FFA and DG and loss of mainly stearic (18:0) and arachidonic (20:4) acids from PIP2. BN52021 pretreatment of ECS-treated mice decreased the accumulation of free palmitic (16:0), 18:0, 20:4, and docosahexaenoic (22:6) acids with no effect on the fatty acids in DG or the loss of PIP2. BN52021 had no effect on basal levels of FFA, DG, or PIP2. One minute of postdecapitation ischemia induced PIP2 loss and accumulation of FFA and DG. BN52021 attenuated the accumulation of free 20:4 and 22:6 acids, decreased the content of oleic (18:1), 20:4, and 22:6 acids in DG, but had no effect on PIP2 loss. These data indicate that BN52021 reduces the injury-induced activation of phospholipase A2 and lysophospholipase, which mediate the accumulation of FFA in brain, while having a negligible effect on phospholipase C-mediated degradation of PIP2.
Birkle
D L
DL
Louisiana State University Medical Center, New Orleans.
Kurian
P
P
Braquet
P
P
Bazan
N G
NG
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002845:Chromatography; D004075:Diglycerides / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004224:Diterpenes; D004597:Electroshock; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010936:Plant Extracts; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D004075:Diglycerides; D004224:Diterpenes; D005230:Fatty Acids, Nonesterified; D046934:Ginkgolides; D007783:Lactones; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010936:Plant Extracts; D010972:Platelet Activating Factor; C045856:ginkgolide B; D004121:Dimethyl Sulfoxide