title: Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to fluoride.
abstract: In an attempt to elucidate the mechanism by which excessive fluoride damages the central nervous system, the effects of exposure of PC12 cells to different concentrations of fluoride for 48 h on nicotinic acetylcholine receptors (nAChRs) were characterized here. Significant reductions in the number of binding sites for both [3H]epibatidine and [125I]alpha-bungarotoxin, as well as a significant decrease in the B(max) value for the high-affinity of epibatidine binding site were observed in PC12 cells subjected to high levels of fluoride. On the protein level, the alpha 3 and alpha 7 subunits of nAChRs were also significantly decreased in the cells exposed to high concentrations of fluoride. In contrast, such exposure had no significant effect on the level of the beta 2 subunit. These findings suggest that selective decreases in the number of nAChRs may play an important role in the mechanism(s) by which fluoride causes dysfunction of the central nervous system.
authors.affiliation: Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Ke-Ren
authors.initials: KR
authors.lastname: Shan
authors.forename: Yi-Guo
authors.initials: YG
authors.lastname: Long
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guan
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000037:antagonists & inhibitors / Q000378:metabolism; D002038:Bungarotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D018722:Nicotinic Agonists / Q000378:metabolism; D016716:PC12 Cells; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D012969:Sodium Fluoride; C082748:epibatidine