Modification of GABA and calcium uptake by lipids in synaptosomes from normoxic and ischemic brain

Abstract

The effects of membrane lipid disturbances induced by ischemia and exogenously added lipids on the uptake of GABA and Ca(2+) were investigated in gerbil brain synaptosomes. Ischemia was produced by bilateral ligation of common carotid arteries in Mongolian gerbil for 10 min. The level of the free fatty acids (FFA) increased significantly in ischemic synaptosomes. Incorporation of [1-(14)C]arachidonate into membrane phosphatidylinositol and phosphatidylcholine was decreased by about 20-35%. Furthermore ischemia exerted an inhibitory effect on GABA uptake but remained without effect on calcium accumulation. Thiopental application in dose of 100 mg per kg body weight 30 min before ischemia caused a protective effect on membrane lipid disturbances induced by ischemia and enhanced GABA uptake. Unsaturated fatty acids (arachidonate and docosahexanoate) in concentration of 10(?5)?10(?4) mol/l and lysocompounds (lysophosphatidylcholine and lysophosphatidylethanolamine) in concentrations higher than 10(?4) mol/l decreased GABA and Ca(2+) uptake in synaptosomes from normoxic brains. No effect was seen with saturated stearic acid. These results suggest that the inhibition of GABA uptake into ischemic synaptosomes resulted from an action of unsaturated fatty acids, arachidonic and docosahexanoic acids which were liberated during ischemia. Moreover the transient higher local concentration of lysophospholipids close to GABA carrier system may also have contributed to the inhibition observed during ischemia.