Output and Effects of Thromboxane Produced by the Liver Perfused with Phorbol Myristate Acetate
- 1 January 1988
- journal article
- research article
- Published by Walter de Gruyter GmbH in Biological Chemistry Hoppe-Seyler
- Vol. 369 (2), 1179-1184
- https://doi.org/10.1515/bchm3.1988.369.2.1179
Abstract
The capacity of the perfused rat liver to produce thromboxane after stimulation by phorbol myristate acetate was examined. A total of 109 .+-. 20 and 155 .+-. 28 pmol/g liver were found in the perfusate and in the bile, respectively, after 40 min. The amount of thromboxane recovered in the perfusate and in the bile accounted for 12.6% of the production calculated from the same number of Kupffer cells in primary cultures, indicating that a major part of thromboxane was taken up and inactivated by hepatocytes. The effect of endogenously synthesized thromboxane on the liver was assessed by using CGS 13080, a thromboxane synthase inhibitor, or BM 13.177, a thromboxane receptor antagonist, 20 nM CGS 13080 in the perfusate inhibited the synthesis of thromboxane and at the same time the elevation of portal pressure and glycogenolysis following administration of phorbol 12-myristate 13-acetate (PMA). The thromboxane receptor antagonist BM 13.177 did not inhibit the synthesis of thromboxane but reduced the PMA-related elevation of portal pressure and glycogenolysis to the same extent (> 60%) as CGS 13080. Sodium nitroprusside, a vasodilator, inhibited the rise in portal pressure caused by PMA to the same extent as CGS 13080 or BM 13.177 but reduced the increase in glycogenolysis only by 25%. These results indicate that thromboxane released by stimulated Kupffer cells of the liver elevates portal pressure and glycogenolysis in the perfused rat liver, although by different mechanisms.This publication has 14 references indexed in Scilit:
- Identification of prostaglandin D2 as the major eicosanoid from liver endothelial and Kupffer cellsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1988
- Rat hepatic sinusoidal endothelial cells in monolayer cultureJournal of Hepatology, 1988
- Net prostaglandin release by perfused rat liver after stimulation with phorbol 12-myristate 13-acetateJournal of Hepatology, 1988
- Effects of Leukotrienes and the Thromboxane A2Analogue U-46619 in Isolated Perfused Rat Liver. Metabolic, Hemodynamic and Ion-Flux ResponsesBiological Chemistry Hoppe-Seyler, 1988
- Studies on synthesis and degradation of eicosanoids by rat hepatocytes in primary cultureJournal of Hepatology, 1987
- Prostaglandin Responses in Isolated Perfused Rat Liver: Ca2⊕and K⊕Fluxes, Hemodynamic and Metabolic EffectsBiological Chemistry Hoppe-Seyler, 1987
- Stimulation of hepatic glycogenolysis by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) via cyclooxygenase productsBiochemical and Biophysical Research Communications, 1985
- Degradation of Prostaglandin E2 in a Primary Culture of Adult Rat Hepatocytes1The Journal of Biochemistry, 1984
- Phorbol esters inhibit alpha1 adrenergic stimulation of glycogenolysis in isolated rat hepatocytesBiochemical and Biophysical Research Communications, 1984
- Characterization of imidazo[1,5-a]pyridine-5-hexanoic acid (CGS 13080) as a selective thromboxane synthetase inhibitor using in vitro and in vivo biochemical modelsBiochemical and Biophysical Research Communications, 1983