Novel CB Receptors

新型CB受体

基本信息

批准号：
7880602
负责人：
Nephi Stella
金额：
$ 28.88万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7880602
关键词：
2-arachidonylglycerol AM 251 AM356 Abbreviations Adipocytes Adipose tissue Agonist Astrocytes Behavioral Binding Binding Proteins Biological Brain CNR2 gene Calcium Cannabinoids Cannabis Cardiovascular system Cell physiology Cells Coupling Disease Endocannabinoids GTP-Binding Proteins Genetic Glutamates Hand Health Hippocampus (Brain)Homeostasis Human Illicit Drugs Immune Immune system In Situ Hybridization Knock-out Ligands Literature Mediating Membrane Microglia Molecular Monoacylglycerol Lipases Mus Nervous system structure Neurodegenerative Disorders Neurons Orphan Peripheral Pharmacology Phospholipase C Phosphorylation Physiological Plants Play Receptor Signaling Reproduction Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role SR 141716A Series Signal Pathway Signal Transduction Synaptic Transmission TRPV1 gene Testis Tetrahydrocannabinol Therapeutic Therapeutic Effect Time Tissues United States adipocyte biology analog anandamide cannabinoid receptor capsazepine endogenous cannabinoid system fatty acid amide hydrolase interest lipoprotein lipase methanandamide mitogen-activated protein kinase p38 neuronal excitability neurotransmission novel palmidrol programs receptor research study response tool transmission process virodhamine

项目摘要

DESCRIPTION (provided by applicant): Cannabinoids are the principal psychoactive component of cannabis, the most commonly used illicit drug in the United States. Going beyond the abuse issues there is also great interest in the possible medicinal use of cannabis and cannabinoids. Furthermore, manipulation of the endogenous cannabinoid system shows great therapeutic promise. While it is known that cannabinoids induce biological effects by engaging CB1 and CB2 receptors, strong experimental evidence suggests that additional cannabinoid receptors exist. We have recently confirmed that the orphan receptor GPR55 constitutes one such novel cannabinoid receptor. Specifically, we found that A9THC, JWH-015 (a synthetic cannabinoid) and methanandamide (a stable endocannabinoid analog) activate phospholipase C, increase intracellular calcium and stimulate p38 MAP kinase phosphorylation in GPR55-expressing HEK293 cells. GPR55 is expressed at high levels throughout the brain, immune system, adipose tissue and testis, as well as in neurons, astrocytes and microglial cells in culture, as assessed by RT-PCR. In this application we describe a plan to fully characterize GPR55 distribution and signaling, and determine its place in mediating the effects of plant-derived, synthetic and endogenous cannabinoids. We will do this by completing the following specific aims: 1. Determining the tissue and cellular distribution of GPR55. 2. Identifying the best pharmacological tools to study GPR55 and elucidating its signaling pathways. 3. Ascertaining how GPR55 regulates neuronal, microglial, and adipocyte functions. The completion of these specific aims will allow us to evaluate the role of GPR55 as an additional cannabinoid receptor, and will provide the necessary pharmacological and molecular tools required to determine its involvement in mediating cannabimimetic effects.

描述（由申请人提供）：大麻素是大麻的主要精神活性成分，大麻是美国最常用的非法药物。超越虐待问题，对大麻和大麻素的可能使用也引起了极大的兴趣。此外，对内源性大麻素系统的操纵显示出巨大的治疗前景。众所周知，大麻素通过参与CB1和CB2受体诱导生物学作用，但强有力的实验证据表明存在其他大麻素受体。我们最近证实，孤儿受体GPR55构成了一种这种新型大麻素受体。具体而言，我们发现A9THC，JWH-015（合成大麻素）和甲烷酰胺（稳定的内源性大麻素类似物）激活磷脂酶C，增加细胞内钙并刺激p38 MAP激酶在GPR55表达HEK293细胞中的p38 MAP激酶磷酸化。 RT-PCR评估，GPR55在整个大脑，免疫系统，脂肪组织和睾丸以及培养中的神经元，星形胶质细胞和小胶质细胞中以高水平表达。在此应用中，我们描述了一个计划，以完全表征GPR55分布和信号传导，并确定其在介导植物来源，合成和内源性大麻素的影响中的位置。我们将通过完成以下特定目标来做到这一点：1。确定GPR55的组织和细胞分布。 2。确定研究GPR55并阐明其信号通路的最佳药理工具。 3。确定GPR55如何调节神经元，小胶质细胞和脂肪细胞功能。这些特定目的的完成将使我们能够评估GPR55作为额外的大麻素受体的作用，并将提供必要的药理和分子工具来确定其参与介导大麻含量效应。