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INHIBITORY EFFECTS OF PERCHLOROETHYLENE ON HUMAN NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.
Bale, A. S., P J. Bushnell, AND T J. Shafer. INHIBITORY EFFECTS OF PERCHLOROETHYLENE ON HUMAN NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Perchloroethylene (PERC) is a volatile organic solvent with a variety of industrial uses. PERC exposure has been shown to cause adverse neurological effects including deficits in vision and memory in exposed individuals. Despite knowledge of these effects, the mechanisms by which PERC may modulate central nervous system function are relatively unknown. Studies with other volatile organic compounds (VOCs) such as alkylbenzenes and 1,1,1-trichloroethane have correlated neurobehavioral changes to modifications in brain receptor function. Specifically, the nicotinic acetylcholine receptor (nAChR), which is important in some forms of cognition and memory, has recently been shown to be sensitive to VOCs, including toluene, as well as volatile anesthetic gases. Therefore, we examined whether nAChRs were sensitive to PERC. Using two-electrode voltage clamp techniques, acetylcholine-induced currents were measured in recombinant human 4 2 and 7 nAChRs expressed in Xenopus oocytes. PERC (100-500 M) inhibited nAChR function in a concentration-dependent and reversible manner. PERC (500 M) decreased 4 2-mediated acetylcholine responses by 50 percent (n=3) and 7 responses by 60 percent (n=5) compared to control current amplitudes. Toluene (1 mM), an alkylbenzene solvent, was used as a positive control and also inhibited receptor responses ( 4 2, 24.2 percent, n=4; 7, 18.0 percent, n=2) as has been previously shown in rat nAChRs. These results show that nAChRs represent a potential target for solvents such as PERC in the central nervous system and suggest that nAChR inhibition could contribute to neurotoxic effects associated with this compound. Furthermore, the data implies that human nAChRs are more sensitive to inhibition by PERC than toluene. (This is an abstract of a proposed presentation and does not necessarily reflect USEPA policy.)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
NEUROPHYSIOLOGICAL TOXICOLOGY BRANCH