| 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 (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 activates cells in paraventricular nuclei (PVN) reflected by increased gastric motility and induction of the immediate early gene c-fos 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, therefore it was named as "raotilin-related peptide" . Anatomical evidence showed that there are ascending and descending neuronal projections between PVN, BMA and lower brain stem (NTS, DMX), which participate in the regulation of gastric acid secretion and gastrointestinal motility. Moreover, PVN is the center of appetite regulatory web. In previous work, we found that moti 1 inincreases the gastric motility when it was microinjected into PVN inconscious rat. Other researches have reported that central motilin (by i. c. v.)facilitates gastric motility and gastric emptying. However, whetherghrelin/Motilin-related peptide in PVN modulates the motility of stomach andits probable nervous pathway remain to be revealed.Object: To study the central effects of ghrelin on the activity of neuronsin PVN and to investigate the involved neuronal pathway.Methods: 1. Electrophysiological experiment: In 73 rats, extracellularrecordings in vivo were made from PVN using 3-barrel microelectrode. Neuronswere 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): relin, saline (control group) relin,' [D-Lys-3]-GHRP-6 (antagonist for ghrelin-R), to observe the effects of drugs on the neuron discharge. 2. HRP neuronal tracing technique: To investigate neuronal projective pathway between PVN and BMA, retrograde tracing technique (HRP) was used in 8 rats.Results: 1. Data obtained from electrophysiological experiments: (1) In 73 rats, spontaneous discharge was recorded from 131 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. There were 83 neurons in PVN responded to the gastric distension stimulation (GD). 59 of them (59/83, 71. 1%) showed excitatory response to GD classfied as GD-EXC neuron. And 24 of neurons (24/83, 28.9%) inhibited by GD stimulation as GD-INH neurons. (2) A total of 45 GD-responsive neurons was given drugs by pressure microinjection in which 10/14 (71.4%) of GD-INH neurons were inhibited by ghrelin; change ofthe firing rate was -7+7. 07%(P<0. 05) ; 18/31 (58.1%) neurons were excited of 37.07 + 9. 16%( P<0.05). It showed that the gastric mechanorecepor activation and ghrelin action on the neurons studied were in the same direction of the response. (3) In experiment of antagonist of ghrelin receptor applied, firing frequency of 17/26(65.4%) GD-EXC neurons decreased in -57.3 + 6.83% (P<0.05) while 8/12 (66.7%) GD-INH neurons excited by 77. 8?1. 1%( P<0. 05) to the antagonist. Either the excitatory or...
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