Abstract

Cannabinoids have been shown to exert a neuroprotective influence in organophosphorus-induced toxicity. In our study, we examined the effects of the cannabinoid receptor agonist WIN55,212-2 and NMDA receptor agonist NMDA on cell death in the pheochromocytoma cell line PC12 subjected to the action of an organophosphorus compound, diazinon. Diazinon decreased cell viability in a concentration-dependent manner. Following the exposure of PC12 cells to 200 mu M diazinon for 48 h, reductions in cell survival and protein level of CB1 receptors were observed. Treatment of the cells with 0.1 mu M WIN55,212-2 and 100 mu M NMDA prior to diazinon exposure significantly elevated the cell survival level and protein level of CB1 receptors. The cannabinoid antagonist AM251 (1 mu M) did not inhibit the neuroprotection effect induced by WIN55,212-2, indicating that the neuroprotective effect of this agonist was cannabinoid receptor-independent. The NMDA receptor antagonist MK-801 (1 mu M) enhanced diazinon-mediated neurotoxicity suggesting that precisely NMDA receptors may play a protective role.