CART Peptide Regulation of Neuroendocrine Function

描述(由申请人提供)： CART首先被鉴定为一种mRNA转录本，它在大鼠纹状体中表达上调，作为对精神刺激药物的反应。CART多肽广泛分布于中枢神经系统(CNS)，来源于下丘脑表达最丰富的转录本之一。一些研究已经提供了证据，证明CART可能在HPA轴的调节中发挥作用。然而，目前尚不清楚CART是否在垂体水平调节HPA轴的功能，或者是否通过与经典的下丘脑释放因子相互作用来调节HPA轴的激活。因此，表征中枢和外周给药对促肾上腺皮质激素(ACTH)释放的影响将为CART影响HPA轴的潜在机制提供关键信息。第二个感兴趣的领域集中在CART给药对下丘脑促肾上腺皮质激素释放因子(CRF)和加压素(AVP)表达和释放的假定影响。到目前为止，关于可能的CART受体的信息很少；因此，这项提议的最终目标是分离和克隆一个可能的CART受体。这种蛋白质的鉴定将大大提高我们对CART的生理作用的理解。我们提出的研究的总体目标是确定CART调节HPA轴的潜在机制，以了解CART多肽在中枢神经内分泌中心的生理意义。

DESCRIPTION (provided by applicant): CART was first identified as a mRNA transcript that was upregulated in the rat striatum in response to administration of psychostimulant drugs. CART peptides are widely distributed throughout the central nervous system (CNS) and derive from one of the most abundantly expressed hypothalamic transcripts. Several studies have provided evidence that CART may play a role in the regulation of the HPA axis. However, it is not clear whether CART mediates HPA axis function at the level of the pituitary or if CART regulates activation of the HPA axis through interaction with classic hypothalamic releasing factors. Therefore, characterization of the effects of both central and peripheral administration of CART on the regulation of adrenocorticotropic hormone (ACTH) release will provide key information about the underlying mechanisms of CART's effects on the HPA axis. A second area of interest centers on the putative effects of CART administration on the expression and release of corticotropin-releasing factor (CRF) and vasopressin (AVP) in the hypothalamus. To date there has been little information generated on the subject of a putative CART receptor; therefore, a final aim of this proposal is to isolate and clone a putative receptor for CART. Identification of such a protein will greatly enhance our understanding of the physiological role of CART. The overall goal of our proposed research is to determine the underlying mechanisms of CART regulation of the HPA axis to understand the physiological significance of CART peptides in neuroendocrine centers of the CNS.