GPR55在谷氨酸神经元中表达,并在大鼠和小鼠中功能性调节药物摄入和寻找
Yi He1, Hui Shen2, Guo-Hua Bi1,3
1Addiction Biology Unit, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, 21224, USA.
Translational psychiatry
|February 19, 2024
概括
在谷氨酸神经元中激活G蛋白结合受体55 (GPR55),可降低动物中可卡因和尼古丁的自我管理. 这表明GPR55是药物使用障碍的潜在治疗标.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 成研究 研究成研究
背景情况:
- G蛋白结合受体55 (GPR55) 是一个假定的大麻素受体,在物质使用障碍中没有明确的作用.
- 了解GPR55的功能对于开发新的成治疗方法至关重要.
研究的目的:
- 研究GPR55在大脑中的作用及其对吸毒和寻找药物的行为的影响.
- 确定GPR55激活是否可以调节对可卡因和尼古丁的反应.
主要方法:
- RNAscope在位杂交和免疫组织化学,以确定动物大脑中的GPR55表达.
- 包括药物自给和脑刺激奖励在内的行为分析.
- 脑内核中多巴胺和谷氨酸水平的神经化学分析.
主要成果:
- 在动物大脑中,GPR55主要表达在谷氨酸神经元中,而不是多巴胺神经元.
- 用O-1602激活GPR55减少了野生类型小鼠的可卡因和尼古丁自我管理,但不是GPR55-Knockout小鼠.
- GPR55的激活增加了细胞外的谷氨酸,但在核中没有多巴胺.
结论:
- GPR55的激活调节了吸毒和寻找药物的行为,可能是通过一种依赖谷氨酸的机制.
- GPR55代表了物质使用障碍的有前途的治疗标.
相关概念视频
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


