Synthesis of prostaglandin E-2 ethanolamide from anandamide by cyclooxygenase-2

被引:328
作者
Yu, M [1 ]
Ives, D [1 ]
Ramesha, CS [1 ]
机构
[1] ROCHE BIOSCI,DEPT BIOCHEM,INFLAMMATORY DIS UNIT,PALO ALTO,CA 94303
关键词
D O I
10.1074/jbc.272.34.21181
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Because of its structural similarity to polyunsaturated fatty acids, anandamide could serve as substrate for enzymes such as lipoxygenases and cyclooxygenases, which metabolize polyunsaturated fatty acids to potent bioactive metabolites. Here the ability of recombinant human cyclooxygenase-l (hCOX-1) and cyclooxygenase-2 (hCOX-2) to metabolize anandamide was studied. Baculovirus-expressed and -purified hCOX-2, but not hCOX-1, effectively oxygenated anandamide. Reverse phase high pressure liquid chromatography analysis of the products derived from 1-C-14-labeled anandamide showed that the products formed are similar to those formed with arachidonic acid as substrate. The major prostanoid product derived from anandamide was determined by mass spectrometry to be prostaglandin E-2 ethanolamide. Incubation of anandamide with lysates and the intact cell line expressing COX-2 but not that of COX-1 produced prostaglandin E-2 ethanolamide. These results demonstrate the existence of a COX-a-mediated pathway for anandamide metabolism, and the metabolites formed represent a novel class of prostaglandins.
引用
收藏
页码:21181 / 21186
页数:6
相关论文
共 23 条
[1]   PURIFICATION, CHARACTERIZATION AND SELECTIVE-INHIBITION OF HUMAN PROSTAGLANDIN-G/H SYNTHASE-1 AND SYNTHASE-2 EXPRESSED IN THE BACULOVIRUS SYSTEM [J].
BARNETT, J ;
CHOW, J ;
IVES, D ;
CHIOU, M ;
MACKENZIE, R ;
OSEN, E ;
NGUYEN, B ;
TSING, S ;
BACH, C ;
FREIRE, J ;
CHAN, H ;
SIGAL, E ;
RAMESHA, C .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1994, 1209 (01) :130-139
[2]  
BARNETTECURLEY D, 1995, P SOC EXP BIOL MED, V210, P64
[3]   (-)-Delta(9)-Tetrahydrocannabinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylyl cyclase [J].
Bayewitch, M ;
Rhee, RH ;
AvidorReiss, T ;
Breuer, A ;
Mechoulam, R ;
Vogel, Z .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (17) :9902-9905
[4]   Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1 [J].
Bhattacharyya, DK ;
Lecomte, M ;
Rieke, CJ ;
Garavito, RM ;
Smith, WL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (04) :2179-2184
[5]   Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes [J].
Bisogno, T ;
Maurelli, S ;
Melck, D ;
DePetrocellis, L ;
DiMarzo, V .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (06) :3315-3323
[6]   ANANDAMIDE, AN ENDOGENOUS LIGAND OF THE CANNABINOID RECEPTOR, INDUCES HYPOMOTILITY AND HYPOTHERMIA IN-VIVO IN RODENTS [J].
CRAWLEY, JN ;
CORWIN, RL ;
ROBINSON, JK ;
FELDER, CC ;
DEVANE, WA ;
AXELROD, J .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1993, 46 (04) :967-972
[7]   ISOLATION AND STRUCTURE OF A BRAIN CONSTITUENT THAT BINDS TO THE CANNABINOID RECEPTOR [J].
DEVANE, WA ;
HANUS, L ;
BREUER, A ;
PERTWEE, RG ;
STEVENSON, LA ;
GRIFFIN, G ;
GIBSON, D ;
MANDELBAUM, A ;
ETINGER, A ;
MECHOULAM, R .
SCIENCE, 1992, 258 (5090) :1946-1949
[8]  
HAMBERG M, 1967, J BIOL CHEM, V242, P5336
[9]  
HAPSON AJ, 1995, BIOCHIM BIOPHYS ACTA, V1259, P173
[10]  
HOLTZMAN MJ, 1992, J BIOL CHEM, V267, P21438