Abstract

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.