Lipidomic profile of endocannabinoids from neuronal cells

神经元细胞内源性大麻素的脂质组学特征

• 批准号: 7530564
• 负责人: ERIC L BARKER
• 金额: $ 22.88万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7530564
• 关键词: 2-arachidonylglycerol; Acetylcholine; Address; Affect; Agonist; Amides; Anabolism; Anxiety; Attention; Biochemical; Biological; Biological Markers; Blood; Brain; CNR1 gene; Calcium Channel; Cannabinoids; Carbon; Cell Line; Cell Respiration; Cell physiology; Cells; Cerebrospinal Fluid; Cognition; Complex; Convulsions; Development; Disease; Dopamine; Drug Delivery Systems; Endocannabinoids; Enzymatic Biochemistry; Enzymes; Esters; Event; Family; Fatty Acids; Fever; Fingerprint; Future; Glaucoma; Glutamates; Health; Human; Immune system; In Vitro; Investigation; Knowledge; Link; Lipids; Maps; Marijuana; Mass Spectrum Analysis; Measurement; Memory; Metabolic; Metabolism; Methodology; Methods; Molecular; Monitor; Moods; Movement Disorders; Multiple Sclerosis; Neurons; Neurotransmitter Receptor; Neurotransmitters; Obesity; Pain; Pathway interactions; Pattern; Peripheral; Pharmacology; Phase; Physiological; Physiological Processes; Plants; Play; Product Recycling; Production; Proteins; Receptor Activation; Recycling; Relative (related person); Research; Research Design; Role; Sampling; Serotonin; Signal Transduction; Signaling Molecule; Stimulus; System; Tetrahydrocannabinol; Therapeutic Effect; Thin Layer Chromatography; anandamide; arachidonate; base; brain tissue; chemical synthesis; comparative; drug discovery; in vivo; in vivo Model; innovation; insight; long chain fatty acid; metabolomics; neuroprotection; neurotransmission; receptor recycling; research study; response; tool; trafficking

DESCRIPTION (provided by applicant): The broad, long-term objectives of this proposal are to develop new metabolomic methodologies to identify pathways involved with metabolism and biosynthesis of endogenous cannabinoid signaling molecules such as anandamide and 2-arachidonylglycerol (2-AG). Ultimately, these lipidomic strategies can be employed in in vivo or in vitro systems to better understand the profile of endogenous cannabinoids produced under a variety of stimuli. The endogenous cannabinoids are a family of lipid signaling molecules that are typically amides or esters derived from long-chain fatty acids. These compounds have neuromodulatory activity and appear to play a role in multiple physiological processes. The two major endocannabinoids identified in the brain are anandamide (N-arachidonyl- ethanolamide) and 2-AG. The proposed studies are designed to refine the approaches used to study production and recycling of anandamide as well as other putative endogenous cannabinoids. The specific metabolic and biosynthetic pathways linked to certain calcium channels as well as neurotransmitter receptor activation will be explored. The Specific Aims of this project are: 1) To develop and apply specific metabolite fingerprinting and profiling methodology for identifying the lipidomic profile for endogenous cannabinoids, and 2) To determine stimulus-dependent differences in the release of endogenous cannabinoids. The studies will use molecular, biochemical, analytical (thin layer chromatography, mass spectrometry), and lipidomic/ metabolomic approaches. These innovative comparative lipidomic studies will examine in detail the recycling products derived from metabolized anandamide. A better understanding of the mechanisms of endogenous cannabinoid production and release will provide new insight into the system that is acted upon by marijuana. The Public Relevance: This project has direct relevance to human health because the endocannabinoid system is implicated in modulation of memory, mood, cognition, pain, fever, and the immune system. As such, pharmacological manipulation of this system has potentially therapeutic effects in such conditions as convulsions, glaucoma, movement disorders, anxiety, obesity, and multiple sclerosis. Understanding the molecular basis for controlling the production of the endogenous cannabinoids is critical for future drug discovery efforts targeting this system.

描述（由申请人提供）：本提案的广泛、长期目标是开发新的代谢组学方法，以鉴定与内源性大麻素信号分子（如大麻素和2-花生四烯酸甘油（2-AG））的代谢和生物合成相关的途径。最终，这些脂质组学策略可以在体内或体外系统中使用，以更好地了解在各种刺激下产生的内源性大麻素的概况。内源性大麻素是脂质信号传导分子的家族，其通常是衍生自长链脂肪酸的酰胺或酯。这些化合物具有神经调节活性，似乎在多种生理过程中发挥作用。在大脑中鉴定的两种主要内源性大麻素是大麻素（N-花生四烯酸-乙醇酰胺）和2-AG。拟议的研究旨在改进用于研究anandamide以及其他假定的内源性大麻素的生产和回收的方法。将探讨与某些钙通道以及神经递质受体激活相关的特定代谢和生物合成途径。该项目的具体目的是：1）开发和应用特定的代谢物指纹图谱和分析方法，用于鉴定内源性大麻素的脂质组学特征，2）确定内源性大麻素释放的刺激依赖性差异。研究将使用分子、生物化学、分析（薄层色谱法、质谱法）和脂质组学/代谢组学方法。这些创新的比较脂质组学研究将详细检查来自代谢anandamide的回收产物。更好地了解内源性大麻素产生和释放的机制将为大麻作用的系统提供新的见解。公共相关性：该项目与人类健康直接相关，因为内源性大麻素系统涉及记忆，情绪，认知，疼痛，发烧和免疫系统的调节。因此，该系统的药理学操作在诸如惊厥、青光眼、运动障碍、焦虑、肥胖和多发性硬化症的病症中具有潜在的治疗效果。了解控制内源性大麻素产生的分子基础对于未来针对该系统的药物发现工作至关重要。