Abstract
The effect of acetylglyceryl ether phosphorylcholine (AGEPC) on glycogenolysis and phosphatidylinositol 4,5-bisphosphate has been studied in rat hepatocytes. Previously, this laboratory demonstrated that AGEPC stimulated glucose output from the perfused rat liver and promoted the breakdown of phosphoinositides in rat hepatocytes (Shukla, S. D., Buxton, D. B., Olson, M.S., and Hanahan, D.J. (1983) J. Biol. Chem. 258, 10212-10214). In the present study, addition of AGEPC (10(-13) to 10(-9) M) to rat hepatocytes failed to stimulate glucose output, whereas epinephrine (10(-5)M) and glucagon (10(-7)M) stimulated glucose output by 100% or more in these same cells. The effects of AGEPC, epinephrine, vasopressin, and glucagon on glycogen phosphorylase activity and the breakdown of phosphatidylinositol 4,5-bisphosphate were compared in hepatocytes. AGEPC (10(-9)M) promoted the breakdown of phosphatidylinositol 4,5-bisphosphate in a fashion similar to epinephrine (10(-5)M) and vasopressin (10(-7)M). In contrast to the two calcium-mobilizing hormones, epinephrine and vasopressin, AGEPC did not cause an activation of glycogen phosphorylase. Glucagon activation of glycogen phosphorylase was not accompanied by a significant effect on phosphatidylinositol 4,5-bisphosphate hydrolysis. Thus, AGEPC is a chemical mediator which induces the degradation of phosphatidylinositol 4,5-bisphosphate without activating glycogenolysis in hepatocytes.
Highlights
The data presented in this report show quite conclusively that acetylglyceryl ether phosphorylcholine (AGEPC) does not activate glycogenolysis in isolated rat hepatocytes contrary to its potent glycogenolyticeffect in the perfused rat liver [18, 19]
Consideration of the first alternative explanation would be limited to post-“receptor’’ changes in the cell or the occurrence of subpopulations of AGEPC “receptors”, i.e. some controlling phosphoinositide breakdown and some controlling glycogenolysis
The preparationsof hepatocytes used in this study display typical glycogenolytic responses to calcium-mobilizing hormones as well asto glucagon, a CAMP-elevating hormone
Summary
Experiments were conducted to test the effect of AGEPC on glucose output in hepatocyte suspensions. Fig. 1indicatesthataddition of AGEPC failed to stimulate glucose output at any concentration tested. Addition of either glucagon or epinephrine to incubated hepatocytes resulted in stimulation of glucose output by 100% or more (Fig. 1). M AGEPC failed to activateglycogen phosphorylase in hepatocytes during an 11-min time course study These AGEPC concentrations are 5 and 500 times greater, respectively, than concentrations required toproduce potent effects on glycogenolysis inthe perfused rat liver [18, 19]. The differential effect of AGEPC and epinephrine on glycogen phosphorylase is in contrasttotheir similar stimulating effects on thebreakdown of phosphatidylinositol 4-phosphate andphosphatidylinositol 4,5-bisphosphate in the hepatocyte [18,34]. 3 indicate the effects of AGEPC, epinephrine,vasopressin, and glucagon on glycogen phosphorylase activity and levels of phosphatidylinositol4,5-bisphosphate in hepatocytesat single time points. Glucagon activated glycogen phosphorylase but had no significant effect on the concentration of phosphatidylinositol 4,5-bisphosphate
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