Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
J Neuroendocrinol. 2009 Nov;21(11):910-20. doi: 10.1111/j.1365-2826.2009.01911.x. Epub 2009 Sep 1.
Ghrelin is an orexigenic peptide discovered in the stomach as a ligand of the orphan G-protein coupled receptor, and participates in the regulation of growth hormone (GH) release. Previous studies have demonstrated that ghrelin suppressed water intake and stimulated the secretion of arginine vasopressin in rats. We examined the effect of ghrelin on the excitatory synaptic inputs to the magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) using whole-cell patch-clamp recordings in in vitro rat and mouse brain slice preparations. The application of ghrelin (10(-7) approximately 10(-6) m) caused a significant increase in the frequency of the miniature excitatory postsynaptic currents (mEPSCs) in a dose-related manner without affecting the amplitude. The increased frequency of the spontaneous EPSCs persisted in the presence of tetrodotoxin (1 microM). Des-n-octanoyl ghrelin (10(-6) m) did not have a significant effect on the mEPSCs. The ghrelin-induced potentiation of the mEPSCs was significantly suppressed by previous exposure to the transient receptor potential vanilloid (TRPV) blocker, ruthenium red (10 microM) and GH secretagougue type 1a receptor selective antagonist, BIM28163 (10 microM). The effects of ghrelin on the supraoptic MNCs in trpv1 knockout mice were significantly attenuated compared to those in wild-type mice counterparts. These results suggest that ghrelin participates in the regulation of synaptic inputs to the MNCs in the SON via interaction with the GH secretagogue type 1a receptor, and that the TRPV1 channel may be involved in ghrelin-induced potentiation of mEPSCs to the MNCs in the SON.
胃饥饿素是一种在胃中发现的促食欲肽，作为孤儿 G 蛋白偶联受体的配体，参与生长激素 (GH) 释放的调节。先前的研究表明，胃饥饿素抑制水的摄入并刺激大鼠血管加压素的分泌。我们使用离体大鼠和小鼠脑片制备的全细胞膜片钳记录法，研究了胃饥饿素对视上核 (SON) 中的大细胞神经分泌细胞 (MNC) 的兴奋性突触传入的影响。胃饥饿素 (10(-7) 至 10(-6) m) 的应用以剂量相关的方式导致微小兴奋性突触后电流 (mEPSC) 的频率显著增加，而不影响幅度。在存在河豚毒素 (1 microM) 的情况下，自发 EPSC 的频率增加持续存在。去甲酰基胃饥饿素 (10(-6) m) 对 mEPSC 没有显著影响。先前暴露于瞬时受体电位香草酸 (TRPV) 阻断剂钌红 (10 microM) 和 GH 分泌肽 1a 受体选择性拮抗剂 BIM28163 (10 microM) 显著抑制了胃饥饿素诱导的 mEPSC 增强。与野生型小鼠相比，trpv1 敲除小鼠中胃饥饿素对视上核 MNC 的作用明显减弱。这些结果表明，胃饥饿素通过与 GH 分泌肽 1a 受体相互作用参与调节 SON 中 MNC 的突触传入，而 TRPV1 通道可能参与胃饥饿素诱导的 SON 中 MNC 的 mEPSC 增强。
