Inhibition of anandamide hydrolysis in rat brain tissue by (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one

被引：36

作者：

Beltramo, M ^{[1
]}

diTomaso, E ^{[1
]}

Piomelli, D ^{[1
]}

机构：

[1] INST NEUROSCI,SAN DIEGO,CA 92121

来源：

FEBS LETTERS | 1997年 / 403卷 / 03期

关键词：

bromoenol lactone; phospholipase A(2); amidohydrolase; anandamide; cannabinoid;

D O I：

10.1016/S0014-5793(97)00061-6

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：

Anandamide, an endogenous cannabinoid substance, is hydrolyzed by an amidohydrolase activity present in rat brain and liver, We report that the bromoenol lactone, (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BTNP), is a potent inhibitor of this enzyme activity, BTNP prevented anandamide hydrolysis in rat brain microsomes with an IC50 of 0.8+/-0.3 mu M. Kinetic and dialysis experiments indicated that this effect was non-competitive and irreversible, After chromatographic fractionation of the enzyme activity, BTNP was still effective, suggesting that it interacts directly with the enzyme, Anandamide hydrolysis was 12-fold greater in rat cortical neurons (1.94+/-0.1 pmol/min/mg protein) than in cortical astrocytes (0.16+/-0.01 pmol/min/mg protein) and, in either cell type, it,vas inhibited by BTNP (IC50=0.1 mu M in neurons), These results suggest that BTNP may provide a useful lead for the development of novel inhibitors of anandamide hydrolysis. (C) Federation of European Biochemical Societies.

引用

页码：263 / 267

页数：5

共 25 条

[21] THE RELEASE AND UPTAKE OF EXCITATORY AMINO-ACIDS [J].