Dissociation of E prostaglandin effects on liver glycogenolysis and cyclic AMP levels.
Some metabolic effects of prostaglandins have been related to their alteration of adenosine-3',5'-monophosphate (cyclic AMP) metabolism in different tissues. Prostaglandins E1 and E2 stimulate liver adenylate cyclase in vitro, but conflicting reports have been made about metabolic changes caused by E prostaglandins in hepatic tissue. We have attempted to resolve these issues by comparing the effects of PGE1 with those of glucagon using broken-cell homogenates, intact hepatocytes, liver slices and perfused liver. Prostaglandin E1 (PGE1) increased cyclic AMP in liver slices and in perfused liver without increasing glycogenolysis, but PGE1 had no discernible effect on carbohydrate or cyclic AMP metabolism in isolated hepatocytes. Glucagon caused predictable increases in cyclic AMP and glycogenolysis using hepatocytes, liver slices or perfused liver. These data can be explained by the absence of PGE effects on cyclic AMP metabolism in hepatocytes. The concentration of E prostaglandins (PGEs) increased 1.75-fold during incubations (37 degrees C) of hepatocyte suspensions, but cyclic AMP remained constant. Addition of exogenous arachidonate and indomethacin to cell suspensions increased and decreased PGEs, respectively, but cyclic AMP and glycogen metabolism were unchanged. Arachidonate and indomethacin likewise did not alter glucagon-stimulated glycogenolysis or cyclic AMP biosynthesis. The production of E prostaglandins and cyclic AMP appears to be unrelated in hepatocytes.
D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D008112:Liver Glycogen; D011458:Prostaglandins E; D005934:Glucagon; D000242:Cyclic AMP; D000262:Adenylyl Cyclases