Inhibition by 2,4-toluene diisocyanate of the calcium signaling of neuronal nicotinic acetylcholine receptors in human neuroblastoma SH-SY5Y cells.
Toluene diisocyanate (TDI) is widely used as a chemical intermediate in the production of polyurethane products such as foams, coatings, and elastomers. In exposed workers, chronic inhalation of TDI has resulted in significant decreases in lung function. TDI-induced asthma is related to its disturbance of acetylcholine in most affected workers but the actions of TDI on nicotinic acetylcholine receptors (nAChR) are unclear. In order to understand the role of TDI acting on nAChR, we used human neuroblastoma SH-SY5Y cells to investigate the effects of TDI on cytosolic free calcium concentration ([Ca2+]c) changes under the stimulation of nAChR. The results showed that TDI was capable of inhibiting the [Ca2+]c rise induced by nicotinic ligands, epibatidine, DMPP and nicotine. The inhibition was remained, even increased after chronic treatment of TDI. Our study of TDI acting on human nAChR suggests a possibility that the human nerve system plays some role in the toxicity of TDI in the pulmonary system.
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
Yin-Mei
YM
Chiung
Yi-Yun
YY
Kao
Han-Ting
HT
Chen
Pei-Shan
PS
Liu
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D019439:Chromaffin Cells / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013997:Time Factors; D014051:Toluene 2,4-Diisocyanate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D014051:Toluene 2,4-Diisocyanate; C082748:epibatidine; D002118:Calcium