The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats
The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats
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DOI：
10.1053/gast.2002.35954
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发表时间：
2002-10-01
期刊：
影响因子：
29.4
通讯作者：
Nakazato, M
中科院分区：
文献类型：
--
作者：
Date, Y;Murakami, N;Nakazato, M
背景与目的：内脏感觉信息通过传入迷走神经传递到大脑。胃促生长素是一种主要在胃中产生的肽，能刺激进食激素和生长激素（GH）的分泌。胃源性胃饥饿素如何发挥这些中枢作用尚不清楚。在这里，我们确定胃传入迷走神经在胃饥饿素功能中的作用。方法：对迷走神经切开术大鼠静脉注射胃饥饿素或在迷走神经周围注射辣椒素（一种特定的传入神经毒素）后，观察其食物摄取量和生长激素分泌情况。我们通过免疫组化的方法研究了胃饥饿素在这些大鼠神经肽Y （NPY）产生神经元和生长激素释放激素（GHRH）产生神经元中Fos的表达。采用逆转录聚合酶链反应和原位杂交组织化学检测迷走神经传入神经元中胃饥饿素受体的存在。通过I-125-ghrelin与迷走神经的结合研究，确定了ghrelin受体从迷走神经传入神经元向外周的转运。我们记录了胃饥饿素引起的胃迷走神经传入放电，并与胆囊收缩素（CCK）（一种厌食肠肽）的放电进行了比较。结果：阻断胃迷走神经传入可消除胃饥饿素诱导的摄食、生长激素分泌以及产生npy和ghrh的神经元的激活。胃饥饿素受体在迷走神经传入神经元中合成并转运到传入末端。胃饥饿素抑制迷走神经传入的放电，而CCK则刺激它。结论：本研究提示胃迷走神经传入是胃饥饿素向大脑传递饥饿信号和生长激素分泌的主要途径。
Background & Aims: Visceral sensory information is transmitted to the brain through the afferent vagus nerve. Ghrelin, a peptide primarily produced in the stomach, stimulates both feeding and growth hormone (GH) secretion. How stomach-derived ghrelin exerts these central actions is still unknown. Here we determined the role of the gastric afferent vagal nerve in ghrelin's functions. Methods: Food intake and GH secretion were examined after an administration of ghrelin intravenously (IV) to rats with vagotomy or perivagal application of capsaicin, a specific afferent neurotoxin. We investigated Fos expression in neuropeptide Y (NPY)-producing and growth hormone-releasing hormone (GHRH)-producing neurons by immunohistochemistry after administration IV of ghrelin to these rats. The presence of the ghrelin receptor in vagal afferent neurons was assessed by using reverse-transcription polymerase chain reaction and in situ hybridization histochemistry. A binding study on the vagus nerve by I-125-ghrelin was performed to determine the transport of the ghrelin receptor from vagus afferent neurons to the periphery. We recorded the electric discharge of gastric vagal afferent induced by ghrelin and compared it with that by cholecystokinin (CCK), an anorectic gut peptide. Results: Blockade of the gastric vagal afferent abolished ghrelin-induced feeding, GH secretion, and activation of NPY-producing and GHRH-producing neurons. Ghrelin receptors were synthesized in vagal afferent neurons and transported to the afferent terminals. Ghrelin suppressed firing of the vagal afferent, whereas CCK stimulated it. Conclusions: This study indicated that the gastric vagal afferent is the major pathway conveying ghrelin's signals for starvation and GH secretion to the brain.