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Feedback regulation of cannabinoid receptor trafficking and signaling

大麻素受体运输和信号传导的反馈调节

基本信息

批准号：
10312886
负责人：
Joshua Lott
金额：
$ 1.71万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10312886
关键词：
Address Affect Agonist Alternative Splicing Anxiety Area Binding Biological Biology Biosensor Brain CNR1 gene Cannabinoids Cannabis Cell physiology Cell surface Cells Cellular biology Clinical Coupled Desire for food Disease Drug Targeting Drug usage Epilepsy Exhibits Family Feedback Foundations Future G Protein-Coupled Receptor Signaling G-Protein Signaling Pathway G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Genetic Image Intracellular Membranes Investigation Knowledge Learning Ligands Location Medicine Mental Depression Methods Modeling Molecular Conformation Neuraxis Neurobiology Neurologic Neuropharmacology Outcome Pain Permeability Pharmaceutical Preparations Pharmacology Physiological Play Protein Isoforms Proteins Receptor Activation Regulation Research Research Project Grants Resolution Role Signal Pathway Signal Transduction Signaling Protein Site Stimulus Substance abuse problem Surface Testing Therapeutic Therapeutic Agents Therapeutic Human Experimentation Training Translating Variant Work base cannabinoid receptor design experimental study extracellular fluorescence imaging innovation member novel pleiotropism receptor receptor function response side effect skills therapeutic target therapy outcome trafficking

项目摘要

Project Summary Pharmacology is the study of how medicine works to produce a desired therapeutic outcome. As medicines are developed, they are designed to target specific receptors within the body and alter the way cells function. Of these drug targets, G-protein coupled receptors (GPCRs) are the most common, and my research examines how GPCRs function once drugs bind to them. GPCRs alter cellular responses by initiating G-protein signaling. This signaling was thought to occur only at the surface of cells, but emerging research has shown that G-protein signaling occurs within the cell as well. Therefore, it is important to understand how GPCR trafficking to and from subcellular locations impact their overall signaling capabilities. The cannabinoid receptor-1 (CB1) is a GPCR heavily expressed throughout the brain. It plays numerous neurobiological roles and has been a potential drug target in managing appetite, depression, pain and anxiety. However, drugs that bind to CB1, also known as cannabinoids, produce a wide variety of unintended side effects. For example, THC, the psychoactive component of cannabis, is a cannabinoid that is heavily associated with drug use and substance abuse disorders. My research is particularly focused on understanding how cannabinoids that bind to CB1 produce different biological outcomes. I aim to expand their value as promising therapeutic targets by studying how cannabinoids regulate CB1's subcellular activity. Understanding the functional roles of intracellular GPCR signaling is a new and exciting area of pharmacology and therapeutic research where drugs can be specifically designed for intracellular targeting of receptors. This could have significant implications for understanding the varying outcomes of CB1 activation, as CB1 exhibits significant subcellular localization when compared to GPCRs that are most commonly studied. However, the significance of CB1's subcellular localization requires further investigation. The proposed research project will investigate how CB1 is differentially activated by cannabinoids within the brain, while simultaneously delineating the spatial components of CB1 activation. The results gained from completion of this project will provide a framework for developing CB1 as a viable therapeutic target.

项目总结