Title : Cannabinoid CB1 receptor as a target for chlorpyrifos oxon and other organophosphorus pesticides - Quistad_2002_Toxicol.Lett_135_89 |
Author(s) : Quistad GB , Nomura DK , Sparks SE , Segall Y , Casida JE |
Ref : Toxicol Lett , 135 :89 , 2002 |
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. |
PubMedSearch : Quistad_2002_Toxicol.Lett_135_89 |
PubMedID: 12243867 |
Inhibitor | Tribufos |
Quistad GB, Nomura DK, Sparks SE, Segall Y, Casida JE (2002)
Cannabinoid CB1 receptor as a target for chlorpyrifos oxon and other organophosphorus pesticides
Toxicol Lett
135 :89
Quistad GB, Nomura DK, Sparks SE, Segall Y, Casida JE (2002)
Toxicol Lett
135 :89