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.