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Evaluation of nicotinic receptors agonists and antagonists against paraoxon exposed PC12 cells

Hossein Mehrani1, Leila Golmanesh

  • 1Department of Biochemistry, Faculty of Medicine and Chemical Injuries Research center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Environmental Toxicology and Pharmacology
|July 26, 2011
PubMed

Insights

Organophosphate pesticides like paraoxon cause neurotoxicity beyond acetylcholinesterase (AChE) inhibition. This study shows paraoxon reduces nicotinic acetylcholine receptors (nAChRs) in PC12 cells, suggesting antagonists may offer protection.

Area of Science:

  • Neuroscience
  • Toxicology
  • Molecular Biology

Background:

  • Organophosphate (OP) pesticides can cause neurological and neurobehavioral effects not fully explained by acetylcholinesterase (AChE) inhibition.
  • The precise mechanisms underlying OP-induced neurotoxicity require further elucidation, particularly concerning gene expression and receptor function.

Purpose of the Study:

  • To investigate the effects of paraoxon exposure on nicotinic acetylcholine receptors (nAChRs) gene expression and protein levels in PC12 cells.
  • To determine the role of nAChRs in paraoxon toxicity and explore potential protective strategies using agonists and antagonists.

Main Methods:

  • PC12 cells were exposed to 100μM paraoxon for 48 hours.
  • AChE activity was measured.
  • mRNA and protein levels of nAChR subunits (α(4) and β(2)) were quantified using RT-PCR and Western blotting.
  • Cells were co-treated with paraoxon and various nAChR agonists (nicotine, carbamylcholine) and antagonists (mecamylamine, dihydro-β-erythroidine).

Main Results:

  • Paraoxon (100μM) significantly inhibited AChE activity.
  • Paraoxon exposure led to a significant decrease in both α(4) and β(2) nAChR mRNA and protein levels in PC12 cells.
  • Nicotine, mecamylamine, and dihydro-β-erythroidine effectively prevented the paraoxon-induced reduction in nAChR expression, while carbamylcholine showed limited efficacy.

Conclusions:

  • The α(4)β(2) nAChR subtype is implicated in the toxicity of paraoxon.
  • nAChR antagonists demonstrate a potential protective role against organophosphate-induced neurotoxicity.
  • These findings suggest novel therapeutic targets for mitigating organophosphate pesticide poisoning.

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