Effects of lipoxygenase and cyclooxygenase inhibitors on the induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate and isoproterenol in mouse tissues in vivo.

Abstract

I.p. administration of 12-O-tetradecanoylphorbol-13-acetate (TPA) (400 micrograms/kg) caused a remarkable increase in ornithine decarboxylase (ODC) activity in CD-1 mouse liver (8.3-fold), spleen (17.8-fold), kidney (4-fold), lung (7.7-fold) and brain (2.7-fold). TPA induced an increase in ODC activity in liver, spleen and kidney in a dose-dependent manner (100-800 micrograms/kg). The putrescine contents of these tissues were also increased by TPA injection. BW755C, an inhibitor of cyclooxygenase and lipoxygenase, prevented the TPA-induced increase in ODC activity in liver, spleen and kidney in a dose-dependent manner. AA861-a selective lipoxygenase inhibitor, also showed the inhibition of TPA-induced increase in ODC activity in these tissues. Significant inhibition was observed either by BW755C or AA861 at the dose of 30 mg/kg. On the other hand, indomethacin, a selective cyclooxygenase inhibitor, enhanced the TPA-induced increase in ODC activity in these tissues dose-dependently. Significantly enhancement was observed at 3 mg/kg for liver and spleen and 1 mg/kg for kidney. The subcutaneous administration of isoproterenol (1 mg/kg) caused an increase in ODC activity in both liver (11-fold) and spleen (3.4-fold). Both AA861 and BW755C failed to inhibit the isoproterenol-induced increase in ODC activity in these tissues. These results indicate that product(s) of lipoxygenase pathway play an important role in ODC induction caused by TPA in liver, spleen and kidney, while the lipoxygenase pathway does not play an essential role in the isoproterenol-induced increase in ODC activity.