Actions of the insecticide 2 (nitromethylene) tetrahydro-1, 3-thiazine on insect and vertebrate nicotinic acetylcholine receptors

Abstract

The nitromethylene heterocyclic compound 2(nitromethylene)tetrahydro) 1, 3-thiazine (NMTHT) inhibits the binding of [¹²⁵I)α-bungarotoxin to membranes prepared from cockroach (Periplaneta americana) nerve cord and fish (Torpedo californica) electric organ. Electrophysiological studies on the cockroach fast coxal depressor motorneuron (D_f) reveal a dose-dependent depolarization in response to bath-applied NMTHT. Responses to ionophoretic application of NMTHT on to the cell-body membrane of motorneuron D_f are suppressed by bath-applied mecamylamine (1.0 x 10^-4 M) and α-bungarotoxin (1.0 x 10^-7 M). These findings, together with the detection of a reversal potential close to that estimated for acetylcholine, provide evidence for an agonist action of this nitromethylene on an insect neuronal nicotinic acetylcholine receptor. The binding of [³H]H₁₂-histrionicotoxin to Torpedo membranes was enhanced in the presence of NMTHT indicating an agonist action at this vertebrate peripheral nicotinic acetylcholine receptor. NMTHT is ineffective in radioligand binding assays for rat brain GABA_Areceptors, rat brain L-glutamate receptors and insect (Musca domestica) L-glutamate receptors. Partial block of rat brain muscarinic acetylcholine receptors is detected at millimolar concentrations of NMTHT. Thus nitromethylenes appear to exhibit selectivity for acetylcholine receptors and exhibitan agonist action at nicotinic acetylcholine receptors.