THE ROLE OF GHRELIN DURING AGING

描述：(改编自申请人的摘要)本申请针对 关于内源性(Ghrelin)和Ghrelin活性的一些问题 合成(GH释放肽，GHRPs，如MK-0677)的生长配体 激素促分泌受体(GHS-R)及其相互作用的性质。这个 应用的总体目标是阐明GHS-R的生理作用， 尤其是当它与衰老有关的时候。它的前提是大量的 初步数据，并受到一些假设的推动。具体地说，四个目标 建议：1)确定辛酰基对Ghrelin的作用和 它在Ghrelin与GHS-R相互作用中的作用，2)利用位点定向 突变，确定GHS-R结合口袋的特征(S) 与Ghrelin、假定截短的Ghrelin 1-14和合成的GHRP相互作用， 3)确定Ghrelin及其潜在的替代形式是否刺激 下丘脑神经元的活动，并定义下丘脑神经元 对这些配体作出反应，4)确定衰老是否与 Ghrelin活性的下降；那么这种假定的下降是否是由于 Ghrelin酰化活性降低。

DESCRIPTION: (Adapted from the applicant's abstract) This application addresses a number of questions regarding the activity both endogenous (Ghrelin) and synthetic (GH releasing peptide, GHRPs, such as MK-0677) ligands for the Growth Hormone Secretagogue Receptor (GHS-R) and the nature of their interaction. The application has an overall aim of elucidating the physiologic role of GHS-R, especially as it relates to aging. It is predicated on a significant amount of preliminary data, and driven by a number of hypotheses. Specifically, four aims are proposed: 1) determine the function of the octanoyl moiety on Ghrelin and its role in Ghrelin's interaction with the GHS-R, 2) using site directed mutagenesis, determine the characteristics of the GHS-R binding pocket(s) that interact with Ghrelin, a putative truncated Ghrelin 1-14, and synthetic GHRPs, 3) Determine whether Ghrelin and its potential alternate forms stimulate activity in hypothalamic neuron and define the hypothalamic neurons that respond to these ligands and, 4) determine whether aging is associated with a decline in Ghrelin activity; then whether such a putative decline is due to a decrease in Ghrelin acylating activity.