Effects of Toluene Exposure on Signal Transduction : Toluene Reduced the Signaling via Stimulation of Human Muscarinic Acetylcholine Receptor m2 Subtypes in CHO Cells
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概要
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The organic solvent toluene is used widely in industry and is toxic to the central nervous system (CNS). To clarify the mechanisms of CNS toxicity following toluene exposure, especially with respect to the G protein-coupling of receptors, we determined the effects of toluene on the activation of Gi by stimulating human muscarinic acetylcholine receptor m2 subtypes (hm2 receptors) expressed in Chinese hamster ovary (CHO) cells. We first examined whether toluene affects the inhibition of adenylyl cyclase by Gi. The attenuation of forskolin-stimulated cAMP formation by the stimulation of hm2 receptors was reduced in a medium containing toluene. Next, we determined the effects of toluene on carbamylcholine-stimulated [35S]GTPγS binding using membrane fractions of CHO cells expressing hm2 receptors. Carbamylcholine-stimulated [35S]GTPγS binding activity was markedly reduced when assayed using reaction buffers containing toluene. However, carbamylcholine-stimulated [35S]GTPγS binding activity was essentially unchanged following pretreatment of the cells with a toluene-saturated medium prior to membrane isolation. Toluene pretreatment and the toluene itself did not alter the characteristics of the binding of carbamylcholine and [3H]N-methylscopolamine to hm2 receptors. On the contrary of the effect of toluene for [35S]GTPγS binding, the effect of toluene for attenuation of forskolin-stimulated cAMP formation by the stimulation of hm2 receptors was irreversible. These observations indicate that toluene acts as an inhibitor of the signal transduction via hm2 receptor stimulation in CHO cells, and at least two mechanisms exist in the inhibition mechanisms by toluene.
- 社団法人 日本薬理学会の論文
- 2002-07-01
著者
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Haga Tatsuya
Department Of Neurochemistry Faculty Of Medicine University Of Tokyo
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Haga Tatsuya
Department Of Biochemistry Institute For Brain Research Faculty Of Medicine The University Of Tokyo
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Honma Takeshi
Department of Health Effects Research, National Institute of Industrial Health
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Honma Takeshi
Department Of Health Effects Research National Institute Of Industrial Health
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TSUGA Hirofumi
Department of Neurochemistry, Faculty of Medicine, The university of Tokyo
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Tsuga Hirofumi
Department Of Neurochemistry Faculty Of Medicine University Of Tokyo
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Honma T
Department Of Health Effects Research National Institute Of Industrial Health
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Tsuga Hirofumi
Department of Health Effects Research, National Institute of Industrial Health
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