Paraventricular nucleus administration of calcitonin gene-related peptide inhibits food intake and stimulates the hypothalamo-pituitary-adrenal axis
Paraventricular nucleus administration of calcitonin gene-related peptide inhibits food intake and stimulates the hypothalamo-pituitary-adrenal axis
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DOI：
10.1210/en.2002-220902
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
Dhillo, WS;Small, CJ;Bloom, SR
降钙素基因相关蛋白(CGRP)抑制大鼠侧脑室注射后的摄食，刺激下丘脑-垂体-肾上腺(HPA)轴。然而，下丘脑的位置和作用机制尚不清楚。本实验观察了侧脑室旁核(IPVN)注射降钙素基因相关肽(CGRP)对大鼠摄食量和HPA轴的影响，以及CGRP对体外培养的下丘脑神经肽释放的影响。此外，我们还研究了食物剥夺对下丘脑CGRP表达的影响。注射iPVN后1小时，禁食雄性大鼠摄食量呈剂量依赖性减少(生理盐水，5.1+/-0.8g；0.3nmolCGRP，1.1+/-0.5g；P<；0.001 vs生理盐水)。IPVN注射CGRP(8-37)(CGRP(1)受体拮抗剂)对摄食量无影响。然而，预先给予CGRP(8-37)[CGRP(8-37)(10nmoL)/CGRP(0.3nmoL)，3.0+/-0.8g；P<；0.05vs.0.3nmolCGRP]可减轻iPVN CGRP对摄食量的减少。CGRP(100 NM)刺激下丘脑外植体释放α-黑素细胞刺激素、可卡因和安非他明相关转录物、促肾上腺皮质激素释放激素和精氨酸加压素，分别达到基础水平的127+/-19%、148+/-10%、158+/-17%和198+/-21%(P<；0.05比基础水平)，但不改变神经肽Y和刺激物相关蛋白的释放。禁食24小时的大鼠下丘脑CGRP mRNA水平升高至对照组的130+/-8%[CGRP mRNA(任意单位)，4.75+/-0.4；对照组，3.65+/-0.34；P<；0.05]。我们的数据表明，下丘脑室旁核注射CGRP可抑制食物摄取，刺激HPA轴。
Calcitonin gene-related protein (CGRP) inhibits food intake and stimulates the hypothalamo-pituitary-adrenal (HPA) axis after intracerebroventricular injection in rats. However, the hypothalamic site and mechanism of action are unknown. We investigated the effects of intraparaventricular nucleus administration (iPVN) of CGRP on food intake and the HPA axis in rats and the effect of CGRP on the release of hypothalamic neuropeptides in vitro. In addition, we investigated the effects of food deprivation on hypothalamic CGRP expression. CGRP dose-dependently reduced food intake in the first hour after iPVN injection in fasted male rats (saline, 5.1 +/- 0.8 g; 0.3 nmol CGRP, 1.1 +/- 0.5 g; P < 0.001 vs. saline). iPVN injection of CGRP(8-37) (a CGRP(1) receptor antagonist) alone had no effect on food intake. However, the reduction in food intake by iPVN CGRP was attenuated by prior administration of CGRP(8-37) [CGRP(8-37) (10 nmol)/CGRP (0.3 nmol), 3.0 +/- 0.8 g; P < 0.05 vs. 0.3 nmol CGRP]. CGRP (100 nM) stimulated the release of alpha-melanocyte stimulating hormone, cocaine- and amphetamine-related transcript, corticotropin-releasing hormone, and arginine vasopressin from hypothalamic explants to 127 +/- 19%, 148 +/- 10%, 158 +/- 17%, and 198 +/- 21% of basal levels, respectively (P < 0.05 vs. basal), but did not alter the release of either neuropeptide Y or agouti-related protein. Hypothalamic CGRP mRNA levels in 24-h fasted rats were increased to 130 +/- 8% of control levels [CGRP mRNA ( arbitrary units), 4.75 +/- 0.4; controls, 3.65 +/- 0.34; P < 0.05]. Our data suggest that CGRP administered to the PVN inhibits food intake and stimulates the HPA axis.