Effect of nicotine on type 2 deiodinase activity in cultured rat glial cells.
Intracellular generation of triiodothyronine (T3) from thyroxine (T4) by type 2 deiodinase (D2) in the mammalian brain, plays a key role in thyroid hormone action. The presence of D2 in rat astrocytes suggests the importance of glial cells in the regulation of intracellular T3 levels in the rat central nervous system (CNS). To analyze further the factors that regulate D2 activity in the CNS, we investigated the effects of nicotine and of mecamylamine, which inhibits the binding of nicotine with nicotinic acetylcholine receptors, on D2 activity in cultured mixed glial cells of the rat brain. We incubated cultured mixed glial cells obtained from neonatal Wistar rats in the presence of 10 mM dithiothreitol, 2 nM [125I] reverse T3 and 1 mM 6-N-propyl-2-thiouracil for 2 h at 37 degrees C, and the released 125I- was counted in a gamma counter. D2 activity of cultured cells was dependent on the temperature and the amount of protein. The basal D2 activity of rat mixed glial cells was 1.9 +/- 0.2 fmol of I- released/mg protein/h (mean +/- SEM). The addition of 10(-11), 2 x 10(-11), 10(-10), and 10(-9) M nicotine significantly increased D2 activity to approximately 2.2-, 2.4, 3.5- and 2.9-fold the basal level, respectively. D2 activity stimulated by 10(-8) M nicotine (2.5-fold) reached a peak after 9 h incubation. The stimulatory effect of nicotine was completely blocked by 10(-6) M mecamylamine. In conclusion, nicotine increases D2 activity probably via nicotinic acetylcholine receptors, and may influence brain function, at least in part, by affecting thyroid hormone metabolism.
Gondou
A
A
Second Department of Internal Medicine, Kansai Medical University, Osaka, Moriguchi City, Japan.
Toyoda
N
N
Nishikawa
M
M
Yonemoto
T
T
Sakaguchi
N
N
Tokoro
T
T
Inada
M
M
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008464:Mecamylamine / Q000494:pharmacology; D009457:Neuroglia / Q000201:enzymology*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014285:Triiodothyronine, Reverse / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D004229:Dithiothreitol; D007453:Iodide Peroxidase; D007457:Iodine Radioisotopes; D008464:Mecamylamine; D009538:Nicotine; D018733:Nicotinic Antagonists; D014285:Triiodothyronine, Reverse; D000097564:Iodothyronine Deiodinase Type II