Back to Search
Start Over
Inhibition of neuronal nicotinic acetylcholine receptors by the abused solvent, toluene.
- Source :
-
British Journal of Pharmacology . Oct2002, Vol. 137 Issue 3, p375-383. 9p. - Publication Year :
- 2002
-
Abstract
- 1 Toluene is a representative example of a class of industrial solvents that are voluntarily inhaled as drugs of abuse. Previous data from this lab and others has shown that toluene modulates the function of N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA) and glycine receptors at concentrations that do not affect non-NMDA receptors. 2 We utilized two-electrode voltage-clamp and whole cell patch-clamp techniques to assess the effects of toluene on neuronal nicotinic acetylcholine receptors expressed in oocytes and cultured hippocampal neurons. Toluene (50 micro M to 10 mM) produced a reversible, concentration-dependent inhibition of acetylcholine-induced current in Xenopus oocytes expressing various nicotinic receptor subtypes. The alpha4beta2 and alpha3beta2 subunit combinations were significantly more sensitive to toluene inhibition than the alpha4beta4, alpha3beta4 and alpha7 receptors. 3 Receptors composed of alpha4 and beta2(V253F) subunits showed alpha4beta4-like toluene sensitivity while those containing alpha4 and beta4(F255V) subunits showed alpha4beta2-like sensitivity. 4 In hippocampal neurons, toluene (50 micro M to 10 mM) dose-dependently inhibited ACh-mediated responses with an IC(50) of 1.1 mM. 5 Taken together, these results suggest that nicotinic receptors, like NMDA receptors, show a subunit-dependent sensitivity to toluene and may represent an important site of action for some of the neurobehavioural effects of toluene. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TOLUENE
*SOLVENTS
*DRUGS of abuse
*METHYL aspartate
*OVUM physiology
*ACETYLCHOLINE
*ANALYSIS of variance
*CHOLINERGIC receptors
*ANIMAL experimentation
*CELL culture
*COMPARATIVE studies
*CYTOLOGICAL techniques
*DOSE-effect relationship in pharmacology
*HIPPOCAMPUS (Brain)
*RESEARCH methodology
*MEDICAL cooperation
*NEURONS
*OVUM
*PHARMACOLOGY
*PROTEINS
*RATS
*RESEARCH
*VERTEBRATES
*EVALUATION research
*PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 137
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 8692765
- Full Text :
- https://doi.org/10.1038/sj.bjp.0704874