Cannabinoid CB1 receptor as a target for chlorpyrifos oxon and other organophosphorus pesticides.
Toxicol Lett
; 135(1-2): 89-93, 2002 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-12243867
ABSTRACT
Binding of the endocannabinoid anandamide or of Delta(9)-tetrahydrocannabinol to the agonist site of the cannabinoid receptor (CB1) is commonly assayed with [3H]CP 55,940. Potent long-chain alkylfluorophosphonate inhibitors of agonist binding suggest an additional, important and closely-coupled nucleophilic site, possibly undergoing phosphorylation. We find that the CB1 receptor is also sensitive to inhibition in vitro and in vivo by several organophosphorus pesticides and analogs. Binding of [3H]CP 55,940 to mouse brain CB1 receptor in vitro is inhibited 50% by chlorpyrifos oxon at 14 nM, chlorpyrifos methyl oxon at 64 nM and paraoxon, diazoxon and dichlorvos at 1200-4200 nM. Some 15 other organophosphorus pesticides and analogs are less active in vitro. The plant defoliant tribufos inhibits CB1 in vivo, without cholinergic poisoning signs, by 50% at 50 mg/kg intraperitoneally with a recovery half-time of 3-4 days, indicating covalent derivatization. [3H-ethyl]Chlorpyrifos oxon may be suitable for radiolabeling and characterization of this proposed nucleophilic site.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Droga
/
Clorpirifos
/
Organofosfonatos
/
Inseticidas
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article