MECHANISM OF PROSTAGLANDIN-E2-INDUCED GLUCOSE-PRODUCTION IN RAT HEPATOCYTES

Effects of prostaglandin E2(PGE2) on glycogenolysis were examined in rat hepatocytes. In a batch incubation system using isolated hepatocytes, PGE2 increased glucose output dose-dependently. The glycogenolytic effect of PGE2 was detected at a concentration of 10-11 M, and 10-8M PGE2 elicited the maximum glucose output, which was equal to that by glucagon. PGE2 did not increase cAMP at any dose tested (10-11-10-4 M). Instead, PGE2 increased the cytoplasmic free calcium concentration ([Ca2+]c). When the effect of PGE2 on [Ca2+]c was studied in aequorin-loaded cells, the effect of PGE2 on [Ca2+]c was detected at 10-12 M, and the magnitude of the response increased in a dose dependent manner. PGE2 increased [Ca2+]c even in the presence of 1 μM extracellular calcium, suggesting that PGE2 mobilizes calcium from an intracellular pool. In line with these observations, PGE2 increased the production of inositol trisphosphate. Compared with the action of PGE216, 16-dimethyl-PGE2a PGE2 analog, was less potent in stimulating glycogenolysis. These results indicate that PGE2 stimulates gly-cogenolysis by activating the calcium messenger system. © 1990 by The Endocrine Society.