Eicosanoid-mediated increase in glucose and lactate output as well as decrease and redistribution of flow by complement-activated rat serum in perfused rat liver.
Rat serum, in which the complement system had been activated by incubation with zymosan, increased the glucose and lactate output, and reduced and redistributed the flow in isolated perfused rat liver clearly more than the control serum. Heat inactivation of the rat serum prior to zymosan incubation abolished this difference. Metabolic and hemodynamic alterations caused by the activated serum were dose dependent. They were almost completely inhibited by the cyclooxygenase inhibitor indomethacin and by the thromboxane antagonist 4-[2-(4-chlorobenzesulfonamide)-ethyl]-benzene-acetic acid (BM 13505), but clearly less efficiently by the 5'-lipoxygenase inhibitor nordihydroguaiaretic acid and the leukotriene antagonist N-(3-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-propoxy]-4-chlorine-6-meth yl- phenyl)-1H-tetrazole-5-carboxamide sodium salt (CGP 35949 B). Control serum and to a much larger extent complement-activated serum, caused an overflow of thromboxane B2 and prostaglandin F2 alpha into the hepatic vein. It is concluded that the activated complement system of rat serum can influence liver metabolism and hemodynamics via release from nonparenchymal liver cells of thromboxane and prostaglandins, the latter of which can in turn act on the parenchymal cells.
Muschol
W
W
Institut für Biochemie, Georg-August-Universität Göttingen, Federal Republic of Germany.
Püschel
G P
GP
Hülsmann
M
M
Jungermann
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects*; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003170:Complement Pathway, Alternative / Q000502:physiology; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000097:blood; D015777:Eicosanoids / Q000096:biosynthesis* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D006358:Hot Temperature; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood; D015054:Zymosan / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003169:Complement Inactivator Proteins; D015777:Eicosanoids; D007773:Lactates; D019344:Lactic Acid; D013929:Thromboxane B2; D015054:Zymosan; D015237:Dinoprost; D005947:Glucose