Idriss_1986_J.Pharmacol.Exp.Ther_239_279

The effects of the organophosphate compounds diisopropylfluorophosphate (DFP), dimethylphosphoramidocyanidic acid ethyl ester (tabun), O-ethyl S-2 diisopropylaminoethyl-methyl phosphonothiolate (VX) and the carbamate compound 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-ol methylcarbamate (physostigmine) were studied on the metathoracic flexor and extensor tibialis muscles of Locusta migratoria. These anticholinesterase (anti-ChE) agents interacted with pre- and post-synaptic regions of the glutamatergic neuromuscular synapse. In physiological solution, containing normal calcium concentration (2 mM), these agents initiated spontaneous excitatory post-synaptic potentials (EPSPs) and muscle action potentials (APs) alternating with periods of reduced spontaneous activity in which only miniature excitatory postsynaptic potentials (MEPSPs) could be recorded. This spontaneous EPSP and AP firing was influenced by [Ca++]0; at low concentrations, the spontaneous APs were abolished but EPSPs and MEPSPs could still be seen. Further reduction of [Ca++]0 to 0.2 mM abolished EPSP firing and only MEPSPs were recorded. This spontaneous activity, EPSP and AP, was blocked by tetrodotoxin (0.3 microM). Neither nicotinic nor muscarinic antagonists were able to abolish the presynaptic action of these agents. In addition to these presynaptic actions, a decrease of the peak amplitude of the excitatory postsynaptic currents (EPSC) was induced by perfusion with DFP, VX or physostigmine. Only DFP and VX affected the decay time constant of the EPSC. Furthermore, high concentrations of tabun did not affect the EPSP. Both the pre- and postsynaptic effects of these agents were reversible upon washing the preparations. The present results demonstrate a new site of action of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)