Acetylglyceryl ether phosphorylcholine. A potent activator of hepatic phosphoinositide metabolism and glycogenolysis

Abstract

Acetylglyceryl ether phosphorylcholine (AGEPC), or 1-O-Alkyl-2-acetyl-sn-glyceryl 3-phosphorylcholine, has been shown to have a dramatic influence on phosphoinositide metabolism in isolated rat hepatocytes and upon glycogenolysis in the intact perfused rat liver. Addition of 5 X 10(-10) M AGEPC to 32Pi-labeled rat hepatocytes resulted in up to a 30 to 40% decrease in the [32Pi]phosphatidylinositol 4,5-bisphosphate within 10 s. The 32P content of phosphatidylinositol 4-phosphate decreased approximately 25% within 60 s, while a 5 to 8% decrease in [32P]phosphatidylinositol was observed only after 2 to 5 min of incubation of hepatocytes with AGEPC. Infusion of AGEPC (2 X 10(-10) M) into perfused livers resulted in a 3-fold increase in the glucose output in the effluent perfusate within 2 min. Interestingly, when a 500-fold higher concentration, i.e. 1 X 10(-7) M, of 1-O-alkyl-sn-glyceryl 3-phosphorylcholine or the stereoisomer 3-O-alkyl-2-acetyl-sn-glyceryl 1-phosphorylcholine was infused, no increase in the hepatic glucose output was seen. These observations lead to the conclusion that AGEPC exerts a potent influence on the polyphosphoinositide metabolism and glycogenolysis in rat liver and establishes the liver as an ideal system in which to conduct a detailed inquiry into the biochemical mechanism(s) responsible for the biological action of this unusual phospholipid.