INHIBITION BY γ‐HEXACHLOROCYCLOHEXANE OF ACETYLCHOLINE‐STIMULATED PHOSPHATIDYLINOSITOL SYNTHESIS IN CEREBRAL CORTEX SLICES AND OF PHOSPHATIDIC ACID‐INOSITOL TRANSFERASE IN CEREBRAL CORTEX PARTICULATE FRACTIONS 1

—1 γ‐Hexachlorocyclohexane inhibits the ACh‐stimulated synthesis of phosphatidylinositol in guinea pig cerebral cortex slices, as measured either by the incorporation of [2‐ 3 H]inositol or of 32 P. Phosphatidylinositol synthesis in the control slices is not inhibited. 2 The synthesis of phosphatidylinositol from CDP‐diglyceride in cerebral cortex microsomal preparations is inhibited by γ‐hexachlorocyclohexane. The incorporation of [2‐ 3 H]inositol into lipid in the absence of added cytidine nucleotide in these preparations is not inhibited. 3 δ‐Hexachlorocyclohexane profoundly inhibits phosphatide synthesis and phosphate metabolism in cerebral cortex slices both in the presence and absence of ACh. This isomer also inhibits the exchange reaction for the incorporation of [2‐ 3 H]inositol into lipid in the microsomal preparations. 4 α‐, and β‐Hexachlorocyclohexanes do not inhibit either ACh‐stimulated or control synthesis of phosphatidylinositol in cerebral cortex slices; nor do they inhibit the exchange reaction for [2‐ 3 H]inositol incorporation into lipid in the microsomal preparations. 5 The specific effects of γ‐hexachlorocyclohexane are taken as providing evidence that ACh‐stimulated phosphatidylinositol synthesis in cerebral cortex slices probably involves the CDP‐diglyceride pathway. The possibility is discussed that the primary action of ACh in this system is to cause an increased activity of diglyceride kinase to provide phosphatidic acid for this pathway.