Acetylcholinesterase Inhibitors on the Spinal Cord.
Final rept. 1 Feb 86-30 Sep 89,
MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
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This report describes studies on organophosphorus OP inhibitors of acetylcholinesterase AChE in the mammalian spinal cord in which the mechanism and site of action of the OPs on synaptic transmission were studied with selective agonists and antagonists of putative central neurotransmitters. Spinal cords isolated from neonatal rats 5- to 9-days old were hemisected and placed in experimental chambers. Electrodes attached to dorsal and ventral root pairs recorded the monosynaptic MSR and polysynaptic reflexes PSR. The roles of N- methyl-D-aspartate NMDA and non-NMDA receptors in the generation of MSRs and PSRs and in the action of AChE inhibitors were examined. Utilizing specific receptor inhibitors it was found that the AChE inhibitors caused depression through muscarinic, not nicotinic receptors, that oximes antagonize AChE inhibitors by virtue of their anticholinergic actions, and not regeneration of ChE and that thyrotropin releasing hormone can effectively reverse the depression of reflex activity. The facilitation caused by the AChE inhibitors was found to be caused by a block of bicuculline-sensitive inhibition. In addition, it was found that NMDA and non-NMDA receptors are present at synapses between the dorsal root afferent neuron and the excitatory interneuron in the PSR and between the dorsal root afferent neuron and motoneuron of the MSR. Compounds Sarin, Organophosphorus Spinal CW Agents Acetylcholinesterase Inhibitors Physostigmine Diisopropylphosphorofluoridate Soman Tabun NMDA Receptors RAI.
- Anatomy and Physiology