Selective inhibition of gamma-aminobutyric acid type A receptors in human IMR-32 cells by low concentrations of toluene.
Effects of the neurotoxic organic solvent toluene on human neuronal nicotinic acetylcholine (nACh) and gamma-aminobutyric acid type A (GABA(A)) neurotransmitter receptors were investigated in whole-cell voltage-clamped IMR-32 neuroblastoma cells. Ion currents evoked by near maximum effective concentrations of 1 mM acetylcholine (ACh) and 1 mM gamma-aminobutyric acid (GABA) are inhibited by toluene in a concentration-dependent way. Concentration-effect curves of toluene yield IC(50) values of 276+/-26 and 39+/-6 microM and slope factors of 1.4+/-0.2 and 0.8+/-0.1 for inhibition of the ACh- and GABA-induced ion currents, respectively. The results demonstrate the selective inhibition of human GABA(A) receptors by toluene at concentrations comparable with brain concentrations associated with occupational exposure.
Meulenberg
Cécil J W
CJ
Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80176, NL-3508 TD Utrecht, The Netherlands.
Vijverberg
Henk P M
HP
D000109:Acetylcholine / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016273:Occupational Exposure / Q000009:adverse effects; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D012997:Solvents / Q000633:toxicity; D014050:Toluene / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D058787:GABA-A Receptor Antagonists; D007473:Ion Channels; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D012997:Solvents; D014050:Toluene; D000109:Acetylcholine