Arnold Myrtha, Mura Anna, Langhans Wolfgang, Geary Nori
Institute of Animal Sciences, Swiss Federal Institute of Technology Zurich, Schwerzenbach 8603, Switzerland.
J Neurosci. 2006 Oct 25;26(43):11052-60. doi: 10.1523/JNEUROSCI.2606-06.2006.
Ghrelin is unique among gut peptides in that its plasma level increases during fasts and its administration stimulates eating. Although ghrelin physiology has been intensively studied, whether its eating-stimulatory effect arises from endocrine-neural signal transduction at peripheral or central sites remains unresolved. To address this issue, we tested the effects of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method available, on ghrelin-induced eating. SDA was verified with a cholecystokinin satiation test, retrograde labeling of vagal motor neurons in the dorsal motor nucleus of the vagus with fluorogold, and anterograde labeling of vagal afferents in the nucleus tractus solitarius with wheat germ agglutinin-horseradish peroxidase. Intraperitoneal injections of 10-40 microg/kg ghrelin stimulated eating as robustly in rats with verified complete SDA as in sham-operated controls. Ghrelin also stimulated eating in rats with total subdiaphragmatic vagotomies. We also recorded the electrophysiological responses of gastric load-sensitive vagal afferent neurons to intravenous ghrelin. Ghrelin (10 nmol) phasically (0-30 s) increased activity in two of seven gastric load-sensitive fibers in the absence of gastric loads and tonically (5-30 min) increased activity in only one fiber. Ghrelin did not affect any of the eight fibers tested in the presence of 1-3 ml gastric loads. We conclude that although phasic increases in plasma ghrelin may affect the activity of a fraction of gastric load-sensitive vagal afferents, the acute eating-stimulatory effect of intraperitoneal ghrelin does not require vagal afferent signaling.
胃饥饿素在肠道肽中独具特色，其血浆水平在禁食期间会升高，且给予该物质会刺激进食。尽管对胃饥饿素的生理学进行了深入研究，但其促进食作用是源于外周或中枢部位的内分泌 - 神经信号转导仍未得到解决。为解决这一问题，我们测试了膈下迷走神经去传入（SDA），这是目前最完整且选择性最高的迷走神经去传入方法，对胃饥饿素诱导进食的影响。通过胆囊收缩素饱腹感测试、用荧光金对迷走神经背运动核中的迷走运动神经元进行逆行标记以及用小麦胚凝集素 - 辣根过氧化物酶对孤束核中的迷走传入纤维进行顺行标记来验证SDA。腹腔注射10 - 40微克/千克胃饥饿素，在经证实完全SDA的大鼠中刺激进食的效果与假手术对照组一样强烈。胃饥饿素在膈下完全迷走神经切断的大鼠中也能刺激进食。我们还记录了胃负荷敏感迷走传入神经元对静脉注射胃饥饿素的电生理反应。在没有胃负荷的情况下，胃饥饿素（10纳摩尔）在7条胃负荷敏感纤维中的2条中阶段性（0 - 30秒）增加活动，在有1 - 3毫升胃负荷的情况下，胃饥饿素对所测试的8条纤维中的任何一条都没有影响，仅在1条纤维中持续性（5 - 30分钟）增加活动。我们得出结论，尽管血浆胃饥饿素的阶段性增加可能会影响一部分胃负荷敏感迷走传入纤维的活动，但腹腔注射胃饥饿素的急性促进食作用并不需要迷走传入信号。
