L. Xu: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, 266021 Shandong, China.
Exp Physiol. 2014 Jan;99(1):123-35. doi: 10.1113/expphysiol.2013.074716. Epub 2013 Sep 13.
Ghrelin is an acylated peptide originally identified in the rat stomach as the endogenous ligand for growth hormone secretagogue receptor (GHSR) that promotes gastric motility. Our aims were to explore the effects of ghrelin on gastric-distension-sensitive neurons in the hippocampus and the potential for ghrelin to regulate gastric motility through the arcuate nucleus (Arc). Single-unit discharges in the hippocampus were recorded extracellularly, and gastric motility in conscious rats was monitored. The expression of GHSR-1a in the hippocampus was determined by PCR, Western blot and fluo-immunohistochemistry staining. Retrograde tracing and fluo-immunohistochemistry staining were used to determine ghrelin neuron projection. Ghrelin-Fluoro-Gold double-labelled neurons and GHSR-1a expression were observed in the Arc and hippocampus, respectively. There were gastric-distension-sensitive neurons in the hippocampus that could be excited by ghrelin or by electrical stimulation of the Arc. The excitatory effects could be blocked completely or partly by pretreatment with the ghrelin receptor antagonist [d-Lys-3]-GHRP-6. Gastric motility was significantly promoted by the administration of ghrelin into the hippocampus in a dose-dependent manner that could be completely abolished by [d-Lys-3]-GHRP-6. Electrical stimulation of the Arc could promote gastric motility as well. Nevertheless, these effects could be mitigated by pretreatment with [d-Lys-3]-GHRP-6. Electrical lesioning of the hippocampus diminished the excitatory effects on gastric motility that were induced by electrical stimulation the Arc. Our findings suggest that ghrelin plays an important role in promoting gastric motility via the hippocampus. The Arc may be involved in regulation of the influence of the hippocampus on gastric motility.
胃饥饿素是一种酰化肽，最初在大鼠胃中被鉴定为生长激素促分泌素受体 (GHSR) 的内源性配体，可促进胃动力。我们的目的是探讨胃饥饿素对海马中胃扩张敏感神经元的影响，以及胃饥饿素通过弓状核 (Arc) 调节胃动力的潜力。通过细胞外记录海马中的单个神经元放电，并监测清醒大鼠的胃动力。通过 PCR、Western blot 和荧光免疫组化染色确定海马中的 GHSR-1a 表达。逆行追踪和荧光免疫组化染色用于确定胃饥饿素神经元投射。在 Arc 和海马中观察到胃饥饿素-Fluoro-Gold 双标记神经元和 GHSR-1a 表达。海马中有胃扩张敏感神经元，可被胃饥饿素或 Arc 电刺激兴奋。这些兴奋作用可被胃饥饿素受体拮抗剂 [d-Lys-3]-GHRP-6 预处理完全或部分阻断。胃饥饿素在海马中的给药剂量依赖性地显著促进胃动力，[d-Lys-3]-GHRP-6 可完全阻断该作用。Arc 的电刺激也能促进胃动力。然而，这些作用可以通过 [d-Lys-3]-GHRP-6 的预处理来减轻。海马电损伤减轻了 Arc 电刺激诱导的对胃动力的兴奋作用。我们的研究结果表明，胃饥饿素通过海马在促进胃动力中起重要作用。Arc 可能参与调节海马对胃动力的影响。
