THE ROLE OF PKA IN GRPR DESENSITIZATION

PKA 在GRPR 脱敏中的作用

基本信息

批准号：
8997130
负责人：
ZHOUFENG CHEN
金额：
$ 19.06万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8997130
关键词：
Acute Alanine Allergic Contact Dermatitis Animal Model Antihistamines Attenuated Behavioral Biochemical Genetics Bombesin Receptor Calcium Cells Clinical Cyclic AMP-Dependent Protein Kinases Development Disease Foundations G-Protein-Coupled Receptors GRP gene Genetic Models Goals Health Histamine Image Immune system Label Laboratories Lead Mediating Medical Modeling Molecular Mus Mutagenesis Nervous system structure Neurons Nociception Phosphorylation Physiological Protein Dephosphorylation Protein Kinase A Inhibitor Pruritus Receptor Signaling Resistance Role Series Signal Transduction Site Skin Solid Spinal Spinal Cord Stimulus Testing Time Work base chronic itch combinatorial desensitization design effective therapy inhibitor/antagonist insight interdisciplinary approach new therapeutic target novel novel therapeutics receptor receptor function response sensor tool transmission process

项目摘要

DESCRIPTION (provided by applicant): Chronic itch is a presenting sign in numerous diseases associated with the skin, immune and nervous systems. Chronic itch is largely resistant to conventional antihistamines, and few effective therapies are available. In order to develop novel therapeutics against chronic itch, there is a pressing need for identification of signaling mechanisms by which chronic itch is inhibited. We have shown that gastrin-releasing peptide receptor (GRPR) is an important receptor for the development of chronic itch. More recently, we found that PKA activation attenuates itch by inhibiting GRPR function. Aim 1 is to determine whether PKA activation inhibits itch by blockade of GRPR function. Aim 2 is to examine the role of PKA in GRPR phosphorylation. The proposed studies are highly translational because it will provide mechanistic insights into PKA-mediated inhibition of itch transmission and may expand the pool of the targets that might be explored for designing novel PKA activation-based anti-pruritus therapies.

描述（由申请人提供）：慢性瘙痒是与皮肤、免疫和神经系统相关的许多疾病的表现，慢性瘙痒在很大程度上对传统的抗组胺药有抵抗力，并且很少有有效的疗法可用于开发针对慢性瘙痒的新疗法。瘙痒，迫切需要鉴定抑制慢性瘙痒的信号机制。我们已经证明胃泌素释放肽受体（GRPR）是慢性瘙痒发展的重要受体。最近，我们发现 PKA 激活通过抑制 GRPR 功能来减轻瘙痒。目的 1 是确定 PKA 激活是否通过阻断 GRPR 功能来抑制瘙痒。所提出的研究是检查 PKA 的作用。高度转化，因为它将为 PKA 介导的瘙痒传播抑制提供机制见解，并可能扩大可用于设计新型基于 PKA 激活的抗瘙痒药物的靶标库疗法。