You are here:
INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.
Citation:
Bale, A. S., C A. Meacham, T J. Shafer, AND P J. Bushnell. INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS. Presented at Society for Neuroscience, New Orleans, LA, 11/8-12/2003.
Description:
INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.
A.S. Bale*; P.J. Bushnell; C.A. Meacham; T.J. Shafer
Neurotoxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC, USA
Toluene (TOL) and perchloroethylene (PERC) cause adverse neurological effects including deficits in vision and memory in exposed individuals. Recently several studies have suggested effects on ion channel function could underlie these observed adverse behavioral effects. Specifically, the rat nicotinic acetylcholine receptor (nAChR) among other targets, which is linked to cognition and memory, has recently been shown to be sensitive to volatile organic compounds (VOCs) including toluene, as well as volatile anesthetic gases. However, solvent effects on rat ligand-gated ion channels have not been compared to human ligand-gated ion channels. Thus, effects of TOL and PERC were studied with human and rat nAChRs to determine if there is a difference in receptor sensitivity between the two species at this functional level. Acetylcholine-induced currents were measured in recombinant nAChRs expressed in Xenopus oocytes. There was not a significant difference in PERC(0.01-0.50 mM)-induced inhibition between the human and rat types of the 42 and 32 nAChRs. PERC (0.50 mM) inhibited the 42 receptors by 42.0 5.2% (human, n=6) and 52.2 4.5% (rat, n=8). The 32 receptors were inhibited by 62.2 3.8% (human, n=8; IC50,0.19 mM) and 62.4 4.3% (rat, n=8; IC50,0.21 mM) at the same PERC concentration. Conversely, the human 7 receptors (IC50,0.18 mM) were more sensitive to PERC than the rat 7 receptors (IC50, 0.57 mM). Inhibition of the ACh-induced current with toluene (0.1-3 mM) did not vary with any of the receptors. These results show that nAChRs represent a sensitive target for solvents such as PERC and TOL in the central nervous system and suggest that slight differences in solvent sensitivity between rat and human nAChRs could contribute to subtle behavioral differences between the two species. This work does not necessarily reflect EPA policy.