| Background: Ghrelin is a 28-amino acid endogenous peptide recently identified in the secretory granules of X/A-like cells in the rat stomach, which can act on the growth hormone secretagogue receptor to accelerate the secretion of growth hormone. It was identified that ghrelin-immunoreactive cell and its receptor localize in areas of brain, such as hypothalamus (VMH, PVN, ARC), hippocampus, adenohypophysis and so on. Motilin is a 22-amino acid peptide secreted from the upper part of the small intestine, which regulates the interdigestive motility of gastric. It was recognized as a brain-gut peptide since the peptide and its receptor exist in the central nervous system. Previously, we demonstrated that motilin and motilides activate cells in ventromedial hypothalamus nucleus (VMH) reflected by increased gastric motility in conscious rat,which suggests central motilin participates in the regulation of gastric motility. It was reported in 2001 that ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Human ghrelin and human motilin exhibit 36% identity with each other. Moreover, human ghrelin receptor exhibits a remarkable 50% overall identity with human motilin receptor. Anatomical evidence showed that there are ascending and descending neuronal projections between VMH, MD, PVN, ARC, LH, BMA and lower brain stem (NTS, DMX), which participate in the regulation of gastric acid secretion and gastrointestinal motility. As summarized in a classic paper by Stellar, Electrical stimulation of ventromedial hypothalamus nucleus (VMH) cause to suppress food intake, and of biolateral VMH lesion to induce hyperphagia and obesity. So the ventromedial hypothalamic nucleus was identified as the 'satiety centre ' classically. However ,whether ghrelin/motilin-related peptide in VMH modulates the motility of stomach and its probable nervous pathway remain to be revealed.Object: To study the central effects of ghrelin on the activity of visceral sensitive neurons in VMH and to compare the effect of ghrelin and motilin on the same gastric distension-related neuron for revealing the neuronal pathway involved.Methods:1. Electrophysiological experiment: In 70 rats, extracellular recordings in vivo were made from VMH using 3-barrel microelectrode. Neurons were categorized as gastric distension excitatory (GD-E) or inhibitory (GD-I) neurons tested with gastric distension stimulus. Drugs were applied through the 3-barrel microelectrode by a 4-programmable pressure injector (PM2000B, MDI,USA): (1) ghrelin, saline(control group) (2)ghrelin, [D-Lys-3]-GHRP-6 (antagonist for ghrelin-R), to observe the effects of drugs on the neuron discharge.(3)ghrelin, motilin to observe the effects of drugs on the neuron discharge.2. food intake:27 rats with free access to water and food, were microinjected ghrelin and [D-Lys-3]-GHRP-6 into VMH to observe how they affect the cumulative food .Immediately after injections animals were presented with a preweighed amount of chow, and food consumption was measured 4,8,12 and 24 h later. 3.c-fos and orexins immunohistochemistry: Rats were injected ghrelin and [D-Lys-3]-GHRP-6 into VMH. After injection animals were allowed access to food, ninety minutes rats were anesthetized and perfused transcardially. Immunohistochemistry for c-fos and orexins were used to observe the activation of the neurons in the hypothalamus.Results: 1. Data obtained from electrophysiological experiments: (1) In 70 rats, spontaneous discharge was recorded from 123 neurons. The patterns of electric activity of neurons showed in phasic, continuous and single firing 3 types. The frequency of cell firings have been classified as high, intermediate and low frequency group.(2)There were 98 neurons in VMH responded to the gastric distension stimulation (GD). 43 of them (43/98, 43.88%) showed excitatory response to GD classfied as GD-EXC neuron. And 55 of neurons (55/98, 56.12%) inhibited by GD stimulation as GD-INH neurons.(3) A total of 44 GD-responsive neurons were given drugs by pressure microi...
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