Molecular targets for organophosphates in the central nervous system. Midterm report, 18 May 1995-17 November 1996
In this study, the patch-clamp technique was used as an approach to evaluate the pre- and postsynaptic effects of VX and soman on synaptic currents of cultured hippocampal neurons. Compared to control, the frequency of the currents mediated by the activation of GABA or glutamate receptors was increased in a concentration-dependent manner from 200% to 550%, when exposed to VX from 10 nM to 1 pM. The effect of VX was observed in the presence of TTX and atropine, indicating that it was a presynaptic effect unrelated to the activation of muscarinic receptors. In addition, it was found that the dlhydron-B-erythroldine did not prevent or abolished the effects of VX. Because, either soman or acetylcholine at high concentrations, applied for 5 to 10 min to the cultured neurons did not mimic the potentiation of transmitter release induced by VX, it was concluded that the presynaptic effect of VX was unrelated to the inhibition of cholinesterase enzyme. At the concentrations studied, VX and soman did not change the post-synaptic properties of GABAA, NMDA, and AMPA receptors. The effect of VX was markedly reduced when the extracellular calcium was removed, but was unaffected when the calcium channel blocker verapamil was added to the preparation. The present findings shows that VX exerts a presynaptic effect unrelated to cholinesterase enzyme that is unaffected by the common antidote atropine used for treating intoxication with VX.
- Research Organization:
- Maryland Univ., Baltimore, MD (United States). School of Medicine
- OSTI ID:
- 557466
- Report Number(s):
- AD-A-329221/6/XAB; CNN: Contract DAMD17-95-C-5063; TRN: 73440298
- Resource Relation:
- Other Information: PBD: Nov 1996
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effects of triphenyltin on glycinergic transmission on rat spinal neurons
NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice