ALTERED MODULATION BY EXCITATORY AMINO-ACIDS OF CORTICAL PHOSPHATIDYLINOSITOL SYSTEM STIMULATED BY CARBACHOL IN RATS POISONED BY AN ANTICHOLINESTERASE COMPOUND, DIISOPROPYL FLUOROPHOSPHATE

The effects of glutamate and N-methyl aspartate (NMDA) on carbachol-in duced inositol phosphate (IP) accumulation were evaluated in slices of the cerebral cortex of rats treated with diisopropyl fluorophosphate (DFP) for 2 weeks. This induced an about 75% inhibition of cholinester ases. The IP accumulation induced by carbachol (expressed as ratio sti mulated/basal IP content) was lower in DFP rats than in controls when incorporation of [H-3]-myoinositol into membrane phospholipids and the ir hydrolysis were measured (no washing step between labeling and hydr olytic incubation). There were no differences in carbachol induced IP accumulation between control and DFP rats when only phosphoinositide h ydrolysis was determined (hydrolytic incubation of prelabeled washed s lices). When both incorporation of [H-3]-myoinositol and the hydrolysi s were measured, 0.5 mM glutamate and 0.1 mM NMDA caused a significant , about 40%, decrease of carbachol-induced IP accumulation in control rats; the inhibitory effects of glutamate and NMDA were not significan t in DFP rats. When only hydrolytic IP accumulation by carbachol was s tudied, the inhibitory effects of glutamate and NMDA were very similar in control and DFP rats. Additional experiments on inositol phospholi pid synthesis showed a significantly lesser [H-3]-myoinositol incorpor ation (by about 30%) in DFP rats. This may explain the differences bet ween the results obtained by the two methods. The overall data suggest that the attenuation of glutamate and NMDA effects in DFP-rats depend s on a decrease of carbachol-induced IP accumulation or phosphoinositi de synthesis rather than on the EAA specific action. (C) 1994 Intox Pr ess, Inc.