Nitromethylene Heterocycles: Selective Agonists of Nicotinic Receptors in Locust Neurons Compared to Mouse N1E-115 and BC3H1 Cells

Abstract

Effects of six nitromethylene heterocycle (NMH) insecticidal compounds on subtypes of the nicotinic acetylcholine receptor (nAChR) have been investigated by superfusion of the compounds on whole-cell voltage-clamped locust thoracic ganglion neurons, mouse N1E-115 neuroblastoma cells, and mouse BC3H1 muscle cells. In locust neurons all of the NMHs induce transient inward currents resembling ACh-induced inward current. Following the NMH-induced inward current, the ACh-induced inward current is blocked in the continued presence of the NMH. Increasing the concentration of NMHs from 0.1 to 10 μM enhances the amplitude of the NMH-induced inward current as well as the NMH-induced block of ACh-induced inward current. ACh- and NMH-induced inward currents cross-desensitize. Mammalian endplate-type nAChR in BC3H1 cells and mammalian neuronal-type nAChR in N1E-115 cells are much less sensitive to the NMHs compared to locust neuronal nAChRs. At 10 μM, the NMHs partially block the ACh-induced inward currents mediated by the two subtypes of mammalian nAChR, but fail to induce significant agonist effects. It is concluded that the NMH compounds and ACh act at the same population of nAChRs in locust neurons. The NMH compounds are nAChR agonists and selectively interact with insect-type nAChRs. The relation between the blocking effect of NMHs and nAChR desensitization is discussed.