EFFECT OF MORPHINE AND NALORPHINE ON THE METABOLISM OF PHOSPHOLIPIDS IN GUINEA PIG CEREBRAL CORTEX SLICES

¹ National Institute of Mental Health, Addiction Research Center, U.S. Public Health Service, Lexington, Kentucky

Studies were initiated to determine whether morphine and nalorphine would alter phospholipid metabolism in brain tissue. Slices of guinea pig cerebral cortex were incubated in 2 ml of Krebs-Hensleit bicarbonate saline containing 11.1 µmol of glucose for 2 hr at 37°C. Each vessel contained either P₁³², glycerol-1,3-C¹⁴, myo-inositol-C¹⁴ or choline-methyl-C¹⁴. Morphine and nalorphine were added alone or together in final concentrations of 10^-2 to 10^-6 M. The phospholipids were extracted in chloroform-ethanol (1:1, v/v) and chromatographed on silicic acid-impregnated paper using the solvent diisobutyl ketone-acetic acid-water (40:25:5, v/v). Polyphosphoinositides were separated using the solvent phenol-concentrated NH₃ (99:1, v/v). Autoradiograms were prepared and the labeled phospholipid spots were carefully cut out and counted. Morphine and nalorphine (10^-2-l0^-3 M) significantly stimulated the incorporation of P₁³² into lysophosphatidylinositol, phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, phosphatidic acid and diphosphoinositide about 26 to 299% and inhibited the uptake of P₁³² into phosphatidylcholine 46 to 59%. A significant stimulation (24-83%) was still evident for certain phosphatides in the presence of 10^-6 M morphine or 10^-6 M nalorphine. Nalorphine (10^-2-10^-6 M) did not appear to consistently alter the effect of 10^-2 M morphine on phospholipid metabolism. The data obtained with the C¹⁴-labeled precursors were quite similar to data observed with P₁³² The results suggest that D-1,2-diglyceride, an essential intermediate in the biosynthesis of glycerophosphatides, becomes limiting.