Organophosphate and Carbamate Compounds have Pre- and Postjunctional Effects at the Insect Glutamatergic Synapse

摘要

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-trimethylpyrrol (2,3-6Bindol-5-ol methylcarbamate (physostigmine) were studied on the methathoracic 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 micrometers). Neither nicotinic nor muscarinic antagonists were able to abolish the presynaptic action of these agents.