The elmiric acids: biologically active anandamide analogs.

elmiric Acids：具有生物活性的 anandamide 类似物。

基本信息

批准号：
7727687
负责人：
SUMNER HOWARD BURSTEIN
金额：
$ 33.98万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7727687
关键词：
Absence of pain sensation Acids Adverse effects Anabolism Analgesics Anti-Inflammatory Agents Anti-inflammatory Binding Biological Biological Models Brain Calcium ion Cannabinoids Cell Culture Techniques Cell physiology Cells Chemicals Chinese Hamster Ovary Cell Chronic inflammatory pain Data Dependence Development Endocannabinoids Enzymes Exposure to Family Family member Future Gene Silencing Glycine Inflammation Inflammatory Inhibition of Cell Proliferation Injury Intractable Pain Ligands Longevity Mass Spectrum Analysis Measures Mediating Mediator of activation protein Modeling Molecular Names Narcotics Nomenclature Orphan Pain Patients Peritoneal Fluid Pharmaceutical Preparations Physiological Population Procedures Prostaglandins Rattus Reporting Research Support Rheumatoid Arthritis Role Sampling Suggestion System Testing Time Tissues Uncertainty Work addiction analog anandamide base cannabinoid receptor capsaicin receptor cell type drug candidate glycine transporter human GPRC5C protein in vitro Model in vivo inhibitor/antagonist insight interest member receptor response

项目摘要

As chemical entities, lipoamino acids have been known for some time. However, more recently their occurrence and importance in mammalian species has been discovered. They appear to have close relationships with the endocannabinoids not only structurally but also in terms of biological actions. The latter include analgesia, anti-inflammatory effects, inhibition of cell proliferation and calcium ion mobilization. To date about 40 naturally occurring members of this family have been identified and, additionally, several synthetic analogs have been prepared and studied. To facilitate their identity, a nomenclature system has been suggested based on the name elmiric acid (EMA). The prototypic example, N-arachidonoyl glycine does not bind to CBI, however it does inhibit the glycine transporter GLYT2a and also appears to be a ligand for the orphan G-protein-coupled receptor GPRI8. It may also have a role in regulating tissue levels of anandamide by virtue of its inhibitory effect on FAAH the enzyme that mediates inactivation of anandamide. Its concentration in rat brain is several times higher than anandamide supporting its possible role as a physiological mediator. Future studies should be aimed at elucidating the actions of all of the members of this interesting family of molecules and gaining further insight into possible mechanisms of action. A promising use for these compounds would be as narcotic replacement agents.

作为化学实体，脂氨基酸已知已有一段时间了。然而，更多最近，人们发现了它们在哺乳动物物种中的出现和重要性。他们似乎不仅在结构上而且在结构上与内源性大麻素有密切的关系从生物作用来看。后者包括镇痛、抗炎作用、抑制细胞增殖和钙离子动员。迄今为止自然约40 该家族的出现成员已被鉴定，此外，还有一些合成的类似物已被制备和研究。为了便于识别，命名系统已根据名称 elmiric Acid (EMA) 提出建议。原型示例 N-花生四烯酰甘氨酸不与 CBI 结合，但它会抑制甘氨酸转运蛋白 GLYT2a 似乎也是孤儿 G 蛋白偶联受体 GPRI8 的配体。由于其抑制作用，它还可能在调节 anandamide 的组织水平方面发挥作用。对介导 anandamide 失活的 FAAH 酶的影响。其浓度在大鼠大脑比 anandamide 高几倍，支持其可能作为生理介质。未来的研究应该旨在阐明所有的行动这个有趣的分子家族的成员，并进一步了解可能的行动机制。这些化合物的一个有前景的用途是用作麻醉剂替代代理。