THE ROLE OF GHRELIN DURING AGING

描述：（改编自申请人的摘要） 关于内源性（Ghrelin）和 用于生长的合成（GH释放肽，GHRPs，如MK-0677）配体 激素促分泌素受体（GHS-R）及其相互作用的性质。的 本申请的总体目的是阐明GHS-R的生理作用， 特别是当它与衰老有关时。它是基于大量的 初步数据，并由一些假设驱动。具体而言，四个目标 提出：1）确定Ghrelin上辛酰基部分的功能， 其在Ghrelin与GHS-R相互作用中的作用，2）使用位点定向 诱变，确定GHS-R结合口袋的特征， 与Ghrelin（一种假定截短Ghrelin 1-14）和合成GHRPs相互作用， 3)确定Ghrelin及其潜在的替代形式是否刺激 活动的下丘脑神经元，并定义下丘脑神经元， 对这些配体产生反应，4）确定衰老是否与 Ghrelin活性下降;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.