Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to fluoride.
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.
Chen
Jia
J
Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou, PR China.
Shan
Ke-Ren
KR
Long
Yi-Guo
YG
Wang
Ya-Nan
YN
Nordberg
Agneta
A
Guan
Zhi-Zhong
ZZ
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
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D012969:Sodium Fluoride; C082748:epibatidine