Direct Functional Effects of Parathion and Paraoxon on Neuronal Nicotinic and Muscarinic M3 Acetylcholine Receptors

Abstract

The direct effects of two organophosphates, parathion and paraoxon, on nicotinic and muscarinic acetylcholine receptors in cells from different species were investigated, by using the whole-cell voltage clamp technique. The effects of neuronal type nicotinic receptors in mouse N1E-115, human SH-SY5Y and locust thoracic ganglion cells, and on human muscarinic M3 receptors transfected in Chinese hamster ovary (CHO) cells, were analysed. Parathion and paraoxon inhibit acetylcholine-induced nicotinic inward currents at concentrations in the micromblar range. Surprisingly, parathion is a more potent inhibitor than its active acetyl-cholinesterase-inhibiting metabolite, paraoxon. Moderate differences in sensitivity to the blocking action of the organophosphates appear to exist between cells from different species. Both parathion (100nM) and paraoxon (1μM) induce ion currents in M3-transfected CHO cells. They appear to act as agonists on the human muscarinic M3 receptor, affecting the receptors in a different manner to that of acetylcholine.