Effects of toluene exposure on activation of GTP binding-protein in CHO cells

• Published in: Japanese Journal of Pharmacology 1998, Vol.76 (suppl.1), p.205-205
• Main Authors: Tsuga, Hirofumi, Honma, Takeshi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)40930-X

Toluene is one of the most widely used organic solvents in industry and is toxic to the central nervous system (CNS). To clarify the mechanisms of CNS toxicity following tot uene inhalation, especially with respect to G protein-coupling of receptors, we determined the effects of toluene exposure on activation of Gi by stimulating human m2 muscarinic acetylcholine receptors (hm2 receptors) expressed in CHO cells. We first examined whether toluene affects the inhibition of adenylyl cyclase by Gi. Attenuation of folskolin-stimulated cAMP formation by stimulation of hm2 receptors in CHO cells was reduced in medium saturated with toluene. The effects of toluene on carbamylcholine-stimulated [^^35 S]GTPγS binding were also examined using membrane fractions of CHO cells expressing hm2 receptors. Carbamyicholine-stimulated [^^35 S]GTPγS binding activity was essentially unchanged following pretreatment of the cells with toluene-saturated medium for 15 min prior to membrane isolation. However, Carbamylcholine-stimulated [^^35 S]GTPγS binding activity was markedly reduced when assayed using reaction buffers containing toluene. These observations indicate that toluene acts as an inhibitor of hm2 receptor-mediated activation of Gi in CHO cells.