Division of Bio-Information Engineering, Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama City, Toyama 930-8555, Japan.
Peptides. 2011 Aug;32(8):1606-16. doi: 10.1016/j.peptides.2011.07.001. Epub 2011 Jul 7.
Ghrelin promotes growth hormone (GH) secretion and feeding. Recent studies further showed that ghrelin displayed a defending effect against the depressive-like symptoms and affected sleep in animals and humans. Serotonergic system is considered to be implicated in feeding, depression and other mood disorders, and sleep. The dorsal raphe nucleus (DRN) utilizes serotonin (5-HT) as its major neurotransmitter and expresses GH secretagogue receptors (GHS-Rs). Therefore, the present study was carried out to examine the electrophysiological effect of ghrelin on rat DRN neurons in vitro and determine the ionic mechanism involved. Whole-cell recording revealed that ghrelin depolarized DRN neurons dose-dependently in tetrodotoxin-containing artificial cerebrospinal fluid (TTX ACSF). Pretreatment with [D-Lys(3)]-GHRP-6, a selective antagonist for GHS-Rs, antagonized the ghrelin-induced depolarization. The depolarization was significantly reduced in a low-Na(+) TTX ACSF and in a high-K(+) TTX ACSF and was abolished in the combination of both ACSFs, suggesting that the ghrelin-induced depolarization is mediated by a dual ionic mechanism including an increase in nonselective cationic conductance and a decrease in K(+) conductance. The experiments on the reversal potential also supported an involvement of the dual ionic mechanism in the ghrelin-induced depolarization. On the basis of their electrophysiological and pharmacological properties, approximately 80% of DRN neurons were classified as putative 5-HT-containing neurons and ghrelin depolarized 75% of them. These results suggest that DRN neurons, especially 5-HT-containing neurons, might be involved in the neural mechanisms through which ghrelin participates in the development and/or regulation of feeding behavior, sleep-wake states and depressive-like symptoms.
胃饥饿素促进生长激素（GH）的分泌和摄食。最近的研究进一步表明，胃饥饿素对动物和人类的抑郁样症状和睡眠具有保护作用。5-羟色胺能系统被认为与摄食、抑郁和其他情绪障碍以及睡眠有关。中缝背核（DRN）利用 5-羟色胺（5-HT）作为其主要神经递质，并表达生长激素促分泌受体（GHS-Rs）。因此，本研究旨在探讨胃饥饿素对体外大鼠 DRN 神经元的电生理作用，并确定其涉及的离子机制。全细胞膜片钳记录显示，在含有河豚毒素（TTX）的人工脑脊液（TTX ACSF）中，胃饥饿素可剂量依赖性地使 DRN 神经元去极化。选择性 GHS-R 拮抗剂[D-Lys（3）]-GHRP-6 预处理可拮抗胃饥饿素诱导的去极化。在低钠（Na+）TTX ACSF 和高钾（K+）TTX ACSF 中，去极化明显减少，两种 ACSF 联合使用时则完全消除，提示胃饥饿素诱导的去极化是通过包括非选择性阳离子电导增加和 K+电导降低的双重离子机制介导的。反转电位实验也支持双重离子机制参与胃饥饿素诱导的去极化。根据其电生理和药理学特性，约 80%的 DRN 神经元被分类为可能含有 5-HT 的神经元，胃饥饿素使其中 75%的神经元去极化。这些结果表明，DRN 神经元，特别是含有 5-HT 的神经元，可能参与了胃饥饿素参与进食行为、睡眠-觉醒状态和抑郁样症状的发展和/或调节的神经机制。
