Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects.
摘要：
2-Arachidonoylglycerol (2-AG) and anandamide are endocannabinoids that activate the cannabinoid receptors CB1 and CB2. Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that for anandamide is mediated by fatty acid amide hydrolase ( FAAH), and for 2-AG is thought to involve monoacylglycerol lipase (MAGL). FAAH inhibitors produce a select subset of the behavioral effects observed with CB1 agonists, which suggests a functional segregation of endocannabinoid signaling pathways in vivo. Testing this hypothesis, however, requires specific tools to independently block anandamide and 2-AG metabolism. Here, we report a potent and selective inhibitor of MAGL called JZL184 that, upon administration to mice, raises brain 2-AG by eight-fold without altering anandamide. JZL184-treated mice exhibited a broad array of CB1-dependent behavioral effects, including analgesia, hypothermia and hypomotility. These data indicate that 2-AG endogenously modulates several behavioral processes classically associated with the pharmacology of cannabinoids and point to overlapping and unique functions for 2-AG and anandamide in vivo.
展开
关键词：
Animals Mice, Inbred C57BL Mice Piperidines Amidohydrolases Monoacylglycerol Lipases Arachidonic Acids Glycerides Receptor, Cannabinoid, CB2 Behavior, Animal
DOI：
10.1021/jf803215t
被引量：
Springer
Nature
(全网免费下载)
Nature
国家科技图书文献中心
(权威机构)
万方
查看更多
EBSCO
Semantic Scholar
(全网免费下载)
万方医学
掌桥科研
Ingenta
dx.doi.org
Europe PMC
Oxford Univ Press
NCBI
Europe PMC
(全网免费下载)
NCBI
ResearchGate
(全网免费下载)
ResearchGate
ProQuest
EBSCO
EBSCO
Citeseer
(全网免费下载)
EBSCO
broker.edina.ac.uk
(全网免费下载)
scienceopen.com
(全网免费下载)
evidences.carpha.bvsalud.org
pherobase.com
ajpendo.physiology.org
biomedsearch.com
(全网免费下载)
cirm.ca.gov
readcube.com
osti.gov
(全网免费下载)
scienceopen.com
scripps.edu
(全网免费下载)
f1000.com
ukpmc.ac.uk
rstb.royalsocietypublishing.org
deepdyve.com
jlr.org
mendeley.com
fast.hevs.ch
(全网免费下载)
science-open.com
broker.edina.ac.uk
jonathanzlong.com
(全网免费下载)
orca.cf.ac.uk
hyper.ahajournals.org
molecularpain.com
pharmrev.aspetjournals.org
pubfacts.com
www.socolar.com
学术范
学术范
(全网免费下载)
Nature
(全网免费下载)
Semantic Scholar
(全网免费下载)
Europe PMC
(全网免费下载)
ResearchGate
(全网免费下载)
Citeseer
(全网免费下载)
fast.hevs.ch
(全网免费下载)
scienceopen.com
(全网免费下载)
biomedsearch.com
(全网免费下载)
osti.gov
(全网免费下载)
jonathanzlong.com
(全网免费下载)
scripps.edu
(全网免费下载)
学术范
(全网免费下载)
broker.edina.ac.uk
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
引用走势
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
