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Titolo:
Fatty acid amide hydrolase inhibition by neurotoxic organophosphorus pesticides
Autore:
Quistad, CB; Sparks, SE; Casida, JE;
Indirizzi:
Univ Calif Berkeley, Dept Environm Sci Policy & Management, Environm Chem & Toxicol Lab, Berkeley, CA 94720 USA Univ Calif Berkeley Berkeley CA USA 94720 col Lab, Berkeley, CA 94720 USA
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 1, volume: 173, anno: 2001,
pagine: 48 - 55
SICI:
0041-008X(20010515)173:1<48:FAAHIB>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROPATHY TARGET ESTERASE; PHENYLMETHYLSULFONYL FLUORIDE; CANNABINOID RECEPTOR; ANANDAMIDE; ANALOGS; ENZYME; MICE; MECHANISM; RESIDUES; TOXICITY;
Keywords:
anandamide; anandamide amidohydrolase; chlorpyrifos; delayed neurotoxicity; fatty acid amide hydrolase; neuropathy target esterase; oleamide; profenofos; serine hydrolases; tribufos;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Casida, JE Univ Calif Berkeley, Dept Environm Sci Policy & Management, Environm Chem & Toxicol Lab, 114 Wellman Hall, Berkeley, CA 94720 USA Univ Calif Berkeley 114 Wellman Hall Berkeley CA USA 94720 USA
Citazione:
C.B. Quistad et al., "Fatty acid amide hydrolase inhibition by neurotoxic organophosphorus pesticides", TOX APPL PH, 173(1), 2001, pp. 48-55

Abstract

Organophosphorus (OP) compound-induced inhibition of acetyl-cholinesterase(AChE) and neuropathy target esterase explains the rapid onset and delayedneurotoxic effects, respectively, for OP insecticides and related compounds but apparently not a third or intermediate syndrome with delayed onset and reduced limb mobility, This investigation tests the hypothesis that fattyacid amide hydrolase (FAAH), a modulator of endogenous signaling compoundsaffecting sleep (oleamide) and analgesia (anandamide), is a sensitive target for OP pesticides with possible secondary neurotoxicity. Chlorpyrifos oxon inhibits 50% of the FAAH activity (IC50 at 15 min, 25 degreesC, pH 9.0) in vitro at 40-56 nM for mouse brain and liver, whereas methyl arachidonyl phosphonofluoridate, ethyl octylphosphonofluoridate (EOPE), oleyl-4H-1,3,2-benzodioxaphosphorin 2-oxide (oleyl-BDPO), and dodecyl-BDPO give IC50s of 0.08-1.1 nM. These BDPOs and EOPF inhibit mouse brain FAAH in vitro with greater than or equal to 200-fold higher potency than for AChE. Five OP pesticides inhibit 50% of the brain FAAH activity (ED50) at <30 mg/kg 4 h after ip administration to mice; while inhibition by chlorpyrifos, diazinon, and methamidophos occurs near acutely toxic levels, profenofos and tribufos are effective at asymptomatic doses. Two BDPOs (dodecyl and phenyl) and EOPF are potent inhibitors of FAAH in vivo (ED50 0.5-6 mg/kg), FAAH inhibition of <greater than or equal to>76% in brain depresses movement of mice administered anandamide at 30 mg/kg ip, often leading to limb recumbency. Thus, OP pesticides and related inhibitors of FAAH potentiate the cannabinoid activity of anandamide in mice. More generally, OP compound-induced FAAH inhibition and the associated anandamide accumulation may read to reduced limb mobility as a secondary neurotoxic effect, (C) 2001 academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 20:21:51