Nicotinic Receptors of Different Species Exhibit Differential Sensitivities to Nitromethylene and Organophosphate Insecticides

Abstract

The effects of nitromethylene heterocycle (NMH) and organophosphate (OP) insecticides were studied on nicotinic acetylcholine receptors (nAChR) in cultured cells of different species origin, in order to examine the selectivity of these compounds at the level of the target sites. In mouse muscle BC3H1, mouse NIE-115 and human SH-SY5Y neuroblastoma, and locust thoracic ganglion cells, the neurotransmitter, acetylcholine (ACh), induces a similar transient inward current. Dependent on the cell type, the six NMHs acted as agonists and/or antagonists on nAChR. Distinct agonistic effects of NMHs on nAChR are observed on insect neurons only. Further, NMHs potently block nicotinic responses in insects, while mammalian cells are only moderately affected. In all cases, the neuronal type nAChR was more sensitive to blocking than the endplate type nAChR in mammalian cells. Parathion and paraoxon at micromolar concentrations inhibit ACh-induced nicotinic inward currents. The insecticide, parathion, is a 50-fold more potent inhibitor than its acetyl-cholinesterase-inhibiting metabolite, paraoxon. Moderate differences in sensitivity to the blocking action of the OPs appear to exist among cells of different species. The results demonstrate that the experimental approach of fundamental electrophysiology and the use of cell lines are relevant tools for investigating the species specificity of neurotoxic compounds.