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HUMAN ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS EXPRESSED IN XENOPUS OOCYTES ARE INHIBITED BY TRICHLOROETHYLENE.
Citation:
GIDDINGS, R., C. A. MEACHAM, A. BALE, P. J. BUSHNELL, AND TIM J. SHAFER. HUMAN ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS EXPRESSED IN XENOPUS OOCYTES ARE INHIBITED BY TRICHLOROETHYLENE. Presented at International Neurotoxicology Conference, Research Triangle Park, NC, September 11 - 14, 2005.
Description:
Trichloroethylene (TCE) is a volatile organic solvent (VOC) that is used as a metal degreasing agent and in paints and glue. In addition to being a commonly abused inhalant, run-off from hazardous waste sites contain enough TCE and other VOCs to contaminate ground water and nearby water supplies. As with other VOCs, TCE produces neurobehavioral effects such as euphoria, motor incoordination, visual deficits, and memory loss. Studies with VOCs such as alkylbenzenes and 1,1,1-trichloroethane have correlated these neurobehavioral changes to modifications in brain receptor function. Specifically, the �-7 nicotinic acetylcholine receptor (nAChR), which is linked to cognition and memory, has been shown to be inhibited by two other VOCs, toluene (TOL) and perchloroethylene (PERC). Based on the similar properties of these compounds to TCE, it was hypothesized that TCE would act similarly. Xenopus laevis oocytes were injected with human �-7 subunits and the current across the membrane was measured using two electrode voltage clamp. Human �-7 nAChR inhibition by TCE was rapid, reversible, and concentration-dependent. After a 30 second pre-treatment, at 0.25 mM [TCE], �-7 nAChRs were inhibited by 25.7% � 6.2% (n=5) and at 5 mM, by 77.1 % � 3.29% (n=3), and after a two minute washout, receptor function returned to normal. This initial data shows that TCE inhibits the �-7 nAChR, and, like TOL and PERC, acts on the central nervous system to inhibit normal neurological function and potentially damage memory and cognition functions by directly modulating nAChRs. This abstract does not reflect EPA policy.