Hypothalamic neuronal histamine modulates adaptive behavior and thermogenesis in response to endogenous pyrogen.
Homeostatic involvement of hypothalamic neuronal histamine in adaptive behavior and thermogenesis was investigated when interleukin-1 beta (IL-1 beta), one of the endogenous pyrogens, was infused peripherally in rats. IL-1 beta decreased food and water intake and elevated body temperature. Depletion of neuronal histamine in the hypothalamus induced by alpha-fluoromethylhistidine, a suicide inhibitor of the histamine synthesizing enzyme histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the inhibitory effect on water intake, and enhanced its thermogenic effect. Simultaneously IL-1 beta increased activity of HDC and histamine-N-methyltransferase (HMT), a neuronal histamine catabolizing enzyme. Pretreatment with indomethacin completely blocked those increases in turnover of neuronal histamine induced by IL-1 beta. Hypothalamic prostaglandin E2 (PGE2) activated by peripheral IL-1 beta, but not peripheral PGE2, increased both activities of HDC and HMT. Ginsenoside Rg1, a major component of panax ginseng, modulated the suppressive effects of IL-1 beta on ingestive behavior, resulting in a lowering of body temperature. The findings suggest that the effects of IL-1 beta on ingestive behavior and thermogenesis may be modulated by dynamics of hypothalamic neuronal histamine through activation of hypothalamic PGE2 which is elevated by peripheral IL-1 beta.
Sakata
T
T
Department of Internal Medicine I, School of Medicine, Oita Medical University, Japan.
Kang
M
M
Kurokawa
M
M
Yoshimatsu
H
H
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004365:Drugs, Chinese Herbal; D004435:Eating / Q000187:drug effects; D036145:Ginsenosides; D006632:Histamine / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D012503:Saponins / Q000494:pharmacology
D002491:Central Nervous System Agents; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D007375:Interleukin-1; D012503:Saponins; D006632:Histamine; D015232:Dinoprostone; C035054:ginsenoside Rg1