Stimulation of CB1 Cannabinoid and NMDA Receptors Increases Neuroprotective Effect against Diazinon-Induced Neurotoxicity
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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 μM diazinon for 48 h, reductions in cell survival and protein level of CB1 receptors were observed. Treatment of the cells with 0.1 μM WIN55,212-2 and 100 μM NMDA prior to diazinon exposure significantly elevated the cell survival level and protein level of CB1 receptors. The cannabinoid antagonist AM251 (1 μM) 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 μM) enhanced diazinon-mediated neurotoxicity suggesting that precisely NMDA receptors may play a protective role.
Keywordscannabinoids diazinon neuroprotection neurotoxicity PC12 cells viability
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- 10.M. Hashemi, F. Bahrami, H. Sahraei, et al., “The neuroprotective effect of cannabinoid receptor agonist (WIN55,212-2) in paraoxon induced neurotoxicity in PC12 cells and N-methyl-D-aspartate receptor interaction,” Cell J., 12, No. 2, 183-190 (2010).Google Scholar
- 12.J.G. Barbara, N. Auclair, M. P. Roisin, et al., “Direct and indirect interactions between cannabinoid CB1 receptor and group ΙΙ metabotropic glutamate receptor signaling in layer V pyramidal neurons from the rat prefrontal cortex,” Eur. J. Neurosci., 17, No. 5, 981-990 (2003).PubMedCrossRefGoogle Scholar