A selective orexin-1 receptor antagonist reduces food consumption in male and female rats
A selective orexin-1 receptor antagonist reduces food consumption in male and female rats
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DOI：
10.1016/s0167-0115(00)00199-3
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发表时间：
2000-12-22
影响因子：
--
通讯作者：
Arch, JRS
中科院分区：
文献类型：
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作者：
Haynes, AC;Jackson, B;Arch, JRS
各种证据表明食欲素，特别是食欲素-A，在调节食物摄入，但它还没有确定是否这种效果是由食欲素-1或食欲素-2受体介导的。在本研究中，在各种条件下对大鼠腹腔内给予选择性食欲素-1受体拮抗剂1-（2-甲基苯并恶唑-6-基）-3-[1.5]萘啶-4-基脲盐酸盐（SB-334867-A），随后测量24 h内的摄食量。在雄性大鼠中，SB-334867-A（30 mg/kg，i. p.）在光照阶段给予的Orexin-A减少了食欲素-A诱导的食物摄入（7 nmol. i.c.v.）禁食4 h后，再进行喂养刺激。当在黑暗期开始时给药时，24 h内雄性和雌性大鼠的摄食量均减少。在黑暗阶段开始时每日注射3天，在第1天和第3天减少雄性大鼠24 h以上的自然摄食。这些发现证明了用选择性食欲素-1受体拮抗剂直接抑制食欲素-A诱导的食物摄入。此外，抑制夜间进食和食物摄入刺激的过夜快速支持其他证据，食欲素-A参与调节自然进食，并表明食欲素-1受体拮抗剂可能是有用的治疗肥胖症。(C)2000 Elsevier Science B. V.保留所有权利。
A variety of evidence implicates the orexins, especially orexin-A, in the regulation of food intake, but it has not been established whether this effect is mediated by the orexin-1 or orexin-2 receptor. In the present study, a selective orexin-1 receptor antagonist, 1-(2-methylbenzoxazol-6-yl)-3-[1.5]naphthyridin-4-yl urea hydrochloride (SB-334867-A), was administered intraperitoneally to rats under various conditions, and food consumption was subsequently measured over 24 h. In male rats, a single dose of SB-334867-A (30 mg/kg, i.p.) given during the light phase reduced both orexin-A-induced food intake (7 nmol. i.c.v.) and feeding stimulated by an overnight fast for 4 h. When given at the start of the dark phase, food consumption was reduced in both male and female rats over 24 h. Daily injections at the start of the dark phase for 3 days reduced natural feeding in male rats over 24 h on days one and three. These findings demonstrate direct inhibition of orexin-A induced food intake with a selective orexin-1 receptor antagonist. Furthermore, the suppression of nocturnal feeding and food intake stimulated by an overnight fast supports other evidence that orexin-A is involved in the regulation of natural feeding and suggests that orexin-1 receptor antagonists could be useful in the treatment of obesity. (C) 2000 Elsevier Science B.V. All rights reserved.