Peripheral interaction of ghrelin with cholecystokinin on feeding regulation
Peripheral interaction of ghrelin with cholecystokinin on feeding regulation
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DOI：
10.1210/en.2004-1240
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发表时间：
2005-08-01
期刊：
影响因子：
4.8
通讯作者：
Nakazato, M
中科院分区：
文献类型：
--
作者：
Date, Y;Toshinai, K;Nakazato, M
Ghrelin和胆囊收缩素（CCK）是调节摄食的胃肠激素。两者都通过迷走神经传入传递，ghrelin引起饥饿信号，而CCK引起饱足信号。我们研究了生长激素释放肽和CCK功能之间的相互作用，在短期的喂养调节大冢长埃文斯德岛脂肪（OLETF）大鼠，这有一个中断CCK A型受体（CCK-AR），和他们的瘦的同窝出生，长埃文斯德岛大冢（LETO）大鼠。静脉注射ghrelin增加了OLETF和LETO大鼠2小时的食物摄入量。由于OLETF大鼠CCK不敏感，静脉注射CCK可降低LETO大鼠2小时的摄食量，但在OLETF大鼠中则不然。虽然预先给LETO大鼠CCK阻断了ghrelin诱导的摄食，但预先给OLETF大鼠CCK不影响ghrelin诱导的摄食。相反，给LETO大鼠预先给予ghrelin可阻断CCK诱导的摄食减少。在电生理学研究中，一旦胃迷走神经传入放电被胃饥饿素或CCK给药改变，它们不能被CCK或胃饥饿素的连续给药分别另外影响。CCK预处理可减弱ghrelin诱导的下丘脑弓状核Fos表达。利用免疫组织化学，我们还证明了GH促分泌素受体（GHS-R），细胞受体的生长激素释放肽，与CCK-AR在迷走神经传入神经元的共定位。这些结果表明，迷走神经起着至关重要的作用，在确定外周能量平衡。Ghrelin和CCK信号转导的效率可能取决于它们各自血浆浓度的平衡和/或GHS-R和CCK-AR之间的相互作用。
Ghrelin and cholecystokinin (CCK) are gastrointestinal hormones regulating feeding. Both transmitted via the vagal afferent, ghrelin elicits starvation signals, whereas CCK induces satiety signals. We investigated the interaction between ghrelin and CCK functioning in short-term regulation of feeding in Otsuka Long-Evans Tokushima fatty ( OLETF) rats, which have a disrupted CCK type A receptor (CCK-AR), and their lean littermates, Long-Evans Tokushima Otsuka (LETO) rats. Intravenous administration of ghrelin increased 2-h food intake in both OLETF and LETO rats. Because OLETF rats are CCK insensitive, iv-administered CCK decreased 2-h food intake in LETO, but not in OLETF, rats. Although preadministration of CCK to LETO rats blocked food intake induced by ghrelin, CCK preadministration to OLETF rats did not affect ghrelin-induced food intake. Conversely, preadministration of ghrelin to LETO rats blocked feeding reductions induced by CCK. In electrophysiological studies, once gastric vagal afferent discharges were altered by ghrelin or CCK administration, they could not be additionally affected by serial administrations of either CCK or ghrelin, respectively. The induction of Fos expression in the hypothalamic arcuate nucleus by ghrelin was also attenuated by CCK preadministration. Using immunohistochemistry, we also demonstrated the colocalization of GH secretagogue receptor (GHS-R), the cellular receptor for ghrelin, with CCK-AR in vagal afferent neurons. These results indicate that the vagus nerve plays a crucial role in determining peripheral energy balance. The efficiency of ghrelin and CCK signal transduction may depend on the balance of their respective plasma concentration and/or on interactions between GHS-R and CCK-AR.