Involvement of protein kinase C and tyrosine kinase in lipopolysaccharide-induced anorexia.
Injections of lipopolysaccharide (LPS, 3 microg) into the lateral ventricle elicited anorexia with fever and also decreased body weight in rats. The LPS-induced anorexia was inhibited by intracerebroventicular (i.c.v.) injections of anti-interleukin (IL)-1beta antibody (Ab), chelerythrine, genistein and tyrphostin 46, but not by injections of indomethacin. Consecutive injections of orthovanadate and LPS (0.3 microg, a dose of LPS that did not show any effect on food intake, body weight or body temperature) reduced body weight, but did not induce anorexia. On the other hand, injections of IL-1beta (50 ng) did not influence food intake, although they decreased body weight and produced fever. The IL-1beta-induced decrease in body weight was inhibited by injections of genistein, but not by injections of chelerythrine or indomethacin. These findings suggest that the LPS-induced anorexia is independent of hyperthermia and involves IL-1beta generation, tyrosine kinase (TK) and protein kinase C (PKC). This is the first in vivo evidence that activation of TK and PKC induced by LPS is linked to anorexia.
Tsushima
H
H
Department of Pharmacology, Nagoya City University Medical School, Kawasumi, Mizuho-ku, 467-8601, Nagoya, Japan. tsushima@med.nagoya-cu.ac.jp
Mori
M
M
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000201:enzymology*; D001835:Body Weight / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D007213:Indomethacin