Roles of neuropeptides in O,O,S-trimethylphosphorothioate (OOS-TMP)-induced anorexia in mice.
O,O,S-Trimethylphosphorothioate (OOS-TMP), an impurity present in various organophosphorus insecticides, has previously been shown to induce hypophagia. The major goal of this study was to investigate its mechanism of action. Both intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injection transiently induced hypophagia at a dose of 5mg/kg within 6h, without causing lung injury. Hypophagia was accompanied by up-regulation of corticotropin releasing factor (CRF) (2.92+/-0.45 vs. 1.7+/-0.5, at 2h after i.c.v., 3.40+/-1.38 vs. 1.76+/-0.41 at 6h after i.p., P<0.05) in the hypothalamus. After i.c.v. injection, hypophagia recovered by 6h after dosing. At doses higher than 5mg/kg, i.c.v. injection induced continuous hypophagia from 20min to 72h after dosing, accompanied by hypothermia and lung injury. OOS-TMP was considered to induce hypophagia through enhancing expression of CRF.
Huang
Linfang
L
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100000, China.
Toyoshima
Megumi
M
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Asakawa
Akihiro
A
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Inoue
Kayoko
K
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Harada
Kouji
K
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Kinoshita
Tomomi
T
Faculty of Engineering, Kyoto University, Kyoto 606-8510, Japan.
Koizumi
Akio
A
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. Electronic address: koizumi@pbh.med.kyoto-u.ac.jp.
D000818:Animals; D000855:Anorexia / Q000378:metabolism; D001831:Body Temperature; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004952:Esters / Q000737:chemistry; D005247:Feeding Behavior; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000737:chemistry*; D063086:Organothiophosphates / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D004952:Esters; D009479:Neuropeptides; D063086:Organothiophosphates; D012333:RNA, Messenger; C019123:O,O,S-trimethyl phosphorothioate; D003346:Corticotropin-Releasing Hormone