Induction of ornithine decarboxylase in rat liver by phorbol ester is mediated by prostanoids from Kupffer cells.
Administration of phorbol 12-myristate 13-acetate (PMA) to rats in vivo resulted in the induction of ornithine decarboxylase activity in the liver which could be blocked by preinjection of indomethacin, a cyclooxygenase inhibitor. In vitro administration of PMA to primary cultures of rat parenchymal cells did not lead to an induction of ornithine decarboxylase activity. It was investigated to what extent non-parenchymal liver cells could play an intermediary role in the expression of the PMA effect on ornithine decarboxylase activity in parenchymal liver cells. Addition of conditioned medium from PMA-activated Kupffer cells to cultured parenchymal cells led to the induction of ornithine decarboxylase activity in parenchymal cells. This effect was not observed with conditioned medium from untreated Kupffer cells or from Kupffer cells treated with PMA plus indomethacin. Conditioned media from PMA-treated or untreated endothelial liver cells were ineffective in the induction of ornithine decarboxylase activity in parenchymal liver cells. Prostaglandin D2, the main eicosanoid produced by Kupffer cells, was able to stimulate the synthesis of ornithine decarboxylase in parenchymal liver cells (up to 40-fold) in a dose-dependent way. Prostaglandin (PG) D2 appeared to be a more potent inducer of ornithine decarboxylase activity in parenchymal cells than PGE1 and PGE2. It is concluded that intercellular communication inside the liver mediated by prostaglandins derived from activated Kupffer cells may form a mechanism to induce synthesis of specific proteins in parenchymal cells.
Kuiper
J
J
Division of Biopharmaceutics, University of Leiden, The Netherlands.
Kamps
J A
JA
Van Berkel
T J
TJ
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D011453:Prostaglandins; D009955:Ornithine Decarboxylase; D000527:Alprostadil; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2; D007213:Indomethacin