Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization

Détails

ID Serval
serval:BIB_C8744939576C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization
Périodique
J Biol Chem
Auteur⸱e⸱s
Desarnaud F., Cadas H., Piomelli D.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
1995
Peer-reviewed
Oui
Volume
270
Numéro
11
Pages
6030-5
Langue
anglais
Notes
Desarnaud, F
Cadas, H
Piomelli, D
eng
Comparative Study
J Biol Chem. 1995 Mar 17;270(11):6030-5.
Résumé
An amidohydrolase activity present in rat brain microsomes catalyzes the hydrolysis of N-arachidonoyl-[3H]ethanolamine ([3H]anandamide), an endogenous cannabimimetic substance, forming [3H]ethanolamine and arachidonic acid. Amidohydrolase activity is maximal at pH 6 and 8, is independent of divalent cations, has an apparent Km for [3H]anandamide of 12.7 +/- 1.8 microM, and has a Vmax of 5630 +/- 200 pmol/min/mg of protein. Phenylmethylsulfonyl fluoride, a serine protease inhibitor, and p-bromophenacyl bromide, a histidine-alkylating reagent, inhibit the activity, whereas N-ethylmaleimide and various nonselective peptidase inhibitors (EDTA, o-phenanthroline, bacitracin) have no effect. Brain amidohydrolase activity exhibits high substrate specificity for [3H]anandamide; N-gamma-linolenoyl-, N-homo-gamma-linolenoyl-, and N-11,14-eicosadienoyl- are hydrolyzed at markedly slower rates. Moreover, N-11-eicosaenoyl- and N-palmitoyl-[3H]ethanolamine are not hydrolyzed. [3H]Anandamide hydrolysis is inhibited competitively by nonradioactive anandamide and by other N-acylethanolamines with the following rank order of potency: anandamide > N-linoleoyl- = N-cis-linolenoyl- = N-gamma-linolenoyl- = N- homo-gamma-linolenoyl- > N-11,14-eicosadienoyl- > N-oleoyl- > N- docosahexaenoyl- > N-docosatetraenoyl > N-linoelaidoyl- > N-eicosaenoyl- > N- palmitoyl > or = N-elaidoyl- = N-eicosanoyl-ethanolamine = no effect. Amidohydrolase activity is high in liver and brain and low in heart, kidney, intestine, stomach, lung, spleen, and skeletal muscle. Within the central nervous system, highest activity is found in globus pallidus and hippocampus, two regions rich in cannabinoid receptors, and lowest activity is found in brainstem and medulla, where cannabinoid receptors are sparse. The results, showing that brain amidohydrolase activity is selective for anandamide and enriched in areas of the central nervous system with high density of cannabinoid receptors, suggest that this activity may participate in the inactivation of anandamide at its sites of action.
Mots-clé
Amidohydrolases/antagonists & inhibitors/*metabolism, Animals, Arachidonic Acid/metabolism, Arachidonic Acids/metabolism, Binding, Competitive, Brain/*enzymology, Calcium Channel Blockers/metabolism, Cell Fractionation, Endocannabinoids, Ethanolamine, Ethanolamines/metabolism, Kinetics, Microsomes/*enzymology, Molecular Structure, Organ Specificity, Polyunsaturated Alkamides, Rats, Rats, Wistar, Substrate Specificity
Pubmed
Création de la notice
13/11/2017 9:57
Dernière modification de la notice
20/08/2019 15:43
Données d'usage