Prostaglandin D2 mediates the stimulation of glycogenolysis in the liver by phorbol ester.
The tumour-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), when added to the perfused liver, stimulates glycogenolysis 2-fold. This stimulation is not seen when aspirin is present in the perfusion medium. In isolated parenchymal liver cells. PMA is not able to stimulate glycogenolysis, suggesting that its effect on glycogenolysis might be indirect and depends on the presence of the non-parenchymal liver cell types. To test the possible operation of an indirect mechanism, we measured the amount of prostaglandin (PG) D2 in liver perfusates. After addition of PMA, the amount of PGD2 is doubled, in parallel with the increase in glycogenolysis. Glycogenolysis in both isolated parenchymal liver cells and perfused liver could be stimulated by the addition of PGD2. Our data indicate that stimulation of glycogenolysis in the liver by PMA may be mediated by non-parenchymal liver cells, which produce PGD2 in response to PMA. Subsequently PGD2 activates glycogenolysis in the parenchymal liver cells. The intercellular communication inside the liver in response to PMA adds a new mechanism to the complex regulation of glucose homoeostasis by the liver.
Casteleijn
E
E
Center for Bio-Pharmaceutical Sciences, University of Leiden, Sylvius Laboratories, The Netherlands.
Kuiper
J
J
Van Rooij
H C
HC
Kamps
J A
JA
Koster
J F
JF
Van Berkel
T J
TJ
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D004357:Drug Synergism; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D008112:Liver Glycogen; D011457:Prostaglandins D; D005934:Glucagon; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D015230:Prostaglandin D2