Enzymatic pathways that regulate endocannabinoid signaling in the nervous system

被引:428
作者
Ahn, Kay [1 ]
McKinney, Michele K. [2 ,3 ]
Cravatt, Benjamin F. [2 ,3 ]
机构
[1] Pfizer Global & Dev, Groton, CT 06340 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
关键词
D O I
10.1021/cr0782067
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The current state of the four major pathways for endocannabinoid metabolism that includes anandamide degradation, anandamide biosynthesis, 2-AG degradation, and 2-AG biosynthesis have been reviewed. Some of these pathways are relatively well characterized in terms of participating enzymes and the advent of specific research tools to probe their function in vivo. For other pathways, enzymes have been identified, but the specific roles that these proteins play remain to be clarified. Although these metabolic pathways present a unique set of experimental opportunities and challenges, common themes can also be selected from a global review of research into their composition and regulation. These themes include strong correlation between the extent of understanding of a specific metabolic pathway and the quality of genetic and pharmacological tools available to probe its functions; molecular events that occur between endocannabinoid production and degradation; and the discrimination of specific physiological functions for anandamide and 2-AG.
引用
收藏
页码:1687 / 1707
页数:21
相关论文
共 190 条
[1]   Genetic variation in two proteins of the endocannabinoid system and their influence on body mass index and metabolism under low fat diet [J].
Aberle, J. ;
Fedderwitz, I. ;
Klages, N. ;
George, E. ;
Beil, F. U. .
HORMONE AND METABOLIC RESEARCH, 2007, 39 (05) :395-397
[2]   INHIBITION OF MACROPHAGE CA2+-INDEPENDENT PHOSPHOLIPASE A(2) BY BROMOENOL LACTONE AND TRIFLUOROMETHYL KETONES [J].
ACKERMANN, EJ ;
CONDEFRIEBOES, K ;
DENNIS, EA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (01) :445-450
[3]  
AHN K, 2006, Patent No. 2006085196
[4]   Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity [J].
Ahn, Kyunghye ;
Johnson, Douglas S. ;
Fitzgerald, Laura R. ;
Liimatta, Marya ;
Arendse, Andrea ;
Stevenson, Tracy ;
Lund, Eric. T. ;
Nugent, Richard A. ;
Nomanbhoy, Tyzoon K. ;
Alexander, Jessica P. ;
Cravatt, Benjamin F. .
BIOCHEMISTRY, 2007, 46 (45) :13019-13030
[5]   The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases [J].
Alexander, Jessica P. ;
Cravatt, Benjamin F. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (30) :9699-9704
[6]   Mechanism of carbamate inactivation of FAAH: Implications for the design of covalent inhibitors and in vivo functional probes for enzymes [J].
Alexander, JP ;
Cravatt, BF .
CHEMISTRY & BIOLOGY, 2005, 12 (11) :1179-1187
[7]  
[Anonymous], 1986, The pharmacohistory of Cannabis sativa
[8]   Lipid rafts control signaling of type-1 cannabinoid receptors in neuronal cells -: Implications for anandamide-induced apoptosis [J].
Bari, M ;
Battista, N ;
Fezza, F ;
Finazzi-Agrò, A ;
Maccarrone, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (13) :12212-12220
[9]   Critical enzymes involved in endocannabinoid metabolism [J].
Basavarajappa, Balapal S. .
PROTEIN AND PEPTIDE LETTERS, 2007, 14 (03) :237-246
[10]   Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension [J].
Bátkai, S ;
Pacher, P ;
Osei-Hyiaman, D ;
Radaeva, S ;
Liu, J ;
Harvey-White, J ;
Offertáler, L ;
Mackie, K ;
Rudd, MA ;
Bukoski, RD ;
Kunos, G .
CIRCULATION, 2004, 110 (14) :1996-2002