J. Biochem, 1998, Vol. 123, No. 1 142-149
© 1998 Japanese Biochemical Society
research-article |
Modulation of Platelet Activating Factor-Induced Glycogenolysis in the Perfused Rat Liver after Administration of Endotoxin In Vivo1
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* Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University Kita-ku, Sapporo 060
Department of Veterinary Physiology, College of Agriculture, Osaka Prefecture University Sakai, Osaka 593
Third Department of Internal Medicine, Hokkaido University School of Medicine Kita-ku, Sapporo 060
2To whom correspondence should be addressed at: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18-jou, Nishi 9-chome, Kita-ku, Sapporo 060. Tel: +81-11-706-5205, Fax: -81-11-757-0703, E-mail: k-kimura{at}vetmed.hokudai.ac.jp
The effect of endotoxin treatment in vivo on platelet activating factor (PAF)-induced glycogenolysis was studied in the perfused rat liver. The addition of PAF (20 nM) to the perfusate increased glucose production concomitant with suppression of oxygen consumption in control rats without endotoxin treatment. At 6 h after endotoxin administration, PAF caused severe suppression of oxygen consumption, but glucose production was greatly inhibited. At 24 h after endotoxin treatment, PAF caused less suppression of oxygen consumption than the control, and glucose production was partially restored. The metabolic responses in the control rat were abolished by the simultaneous presence of cyclooxygenase- and lipoxygenase-inhibitors. Combined use of leukotriene (LT) D4- and thromboxane (Tx) A2-receptor antagonists inhibited the metabolic responses in the rat given endotoxin 6 h before. The efflux of Tx B2 during PAF-infusion decreased 24 h after endotoxin treatment, and Tx A2 receptor antagonist, but not LT D4 receptor antagonist, prevented the suppression of oxygen consumption. These results suggest that different eicosanoids are involved in PAF-induced glycogenolysis in different stages of endotoxemia, and that LT D4 may also play a role in PAF-induced glycogenolysis.
1This work was supported by a special Grant-in-Aid for promotion of Education and Science in Hokkaido University and grants (nos. 06760263 and 07760282) from the Ministry of Education, Science, Sports and Culture of Japan.