Studies on the Effects of Anticholinesterase Compounds on Functions of Neuroglia
Abstract
The purpose of this work was to determine whether selected anticholinesterase compounds are likely to have effects on normal astroglial function in the mammalian central nervous system (CNS). To do this, we studied the effect of three organophosphates, diisopropyl-fluorophosphonate (DFP), paraoxon, and parathion, and the carbamate physostigmine on the ion transport, volume control, electrophysiological and monoamine transmitter uptake properties of primary astrocyte cultures. Compounds were studied at 1 micrometer -1 mM concentrations and both acute and chronic effects were observed. Physostigmine and parathion inhibited uptake of tritium-labelled serotonin at 10 micrometers, but had no effects at concentrations of 1 micrometer of less. The effects of parathion and paraoxon were irreversible within at least 1 hour after removal of the inhibitor. In conclusion, it seems that some acetylcholinesterase (AChE) inhibitors have marked effects on monoamine transmitter uptake, ion transport, and volume regulation by astrocytes independent of their AChE inhibitor effects. However, the effects are only seen at concentrations of 10 micrometers or greater and thus are unlikely to be related to nonlethal toxic effects of these agents. In addition, increased muscarinic receptor stimulation caused by AChE inhibition-induced increases in ACh levels is also likely to occur on astrocytes, and this would presumably occur at concentrations of AChE inhibitors normally encountered.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1987
- Accession Number
- ADA200182
Entities
People
- Harold K. Kimelberg
Organizations
- Albany Medical College