Effects Of Ghrelin In PVN On Gastric Motility And The Immunoreactive Expression Of Hypothalmic Neuropeptides By Icv Ghrelin In Rats

Background: Ghrelin is a 28 amino acids brain-gut peptides, the frist endogenous natural ligand for the growth hormone secretagogue receptor(GHSs-R), was originally purified from the rat stomach. The serine 3 residue is N-octanoylated and specifically release GH both in vivo and in vitro. Ghrelin - immunoreactive cells were shown to be located in the hypothalamic arcute nucleus,PVN, VMH as well as the stomach. Human ghrelin and human motilin exhibit 36% identity with each other. Moreover, human ghrelin receptor exhitits a remarkable 50% overall identity with human motilin receptor, so people call ghrelin "motilin-related peptide" . Our past studies have found that motilin can increase the gastric motility when administered into PVN. However, the central actions of ghrelin in PVN on the regulation of gastric motility have not been elucidated. Whether ghrelin could be the functional correlate of motilin in the paraventricular nucleus of hypothalamus in rats need to be investigated. In present study: we measured the gastric motility in freely moving rats investigating the effects and the mechanism of microinjection ghrelin into PVN on gastric movement.Objective:To investigate the effects of ghrelin in PVN on gastric motility and itsmechanism in central nervous system.To investigate the influence of central administration of ghrelin on the immunoreactive expression of SS- and orexin-containing cells in the hypothalamus in the rat.Result:(l).The amplitude of gastric motility in conscious rats weredose-dependently increased by microinjection of ghrelin into PVN, and the effects was abolished by vagotomy.(2). The amplitude of gastric motility was decreased by miroinjection of the GHS-R antagonist (D-Lys3-GHRP-6) into PVN.(3). Orexin-immunoreactive(IR) cells were found obviously in LHA and increased in the group of icv ghrelin compared with the group of NS or D-Lys-GHRP-6.(4).SS-immunoreactive(IR) cells were detected in PVN, PEN, HIP,SON,VMH,LHA ect, and SS-IR of PEN increased in the group of icv D-Lys3-GHRP-6 compared with the group of NS or ghrelin.Conclusion:Our results suggest that intra-PVN ghrelin may participate via GHS-R in theregulation of gastric motility by activating the hypothalamus(PVN)-DVC-vagus axis, implying that ghrelin could be related functionally with motilin in the mechanism of central modulation on gastric motility.The increased orexin cells in LHA in the group of icv ghrelin suggests that orexin, ghrelin as orexigenic peptide, may have some cooperativity in gastrointestinal function and energy homeostasis. The influenced of central ghrelin on the activity of SS neurons in the PEN may be in a different mechanism with that on orexin-containing cells in hypothalamus.