TABLE 1

Long-term nicotine treatment modulates α6α4β2* and α6(nonα4)β2* nAChR expression

125I-α-CtxMII competition studies were done using striatal sections from control and nicotine-treated rats or wild-type and α4 nAChR-null mutant mice at different concentrations of E11A. Biphasic inhibition by E11A (data best fit to a two-site model) was obtained in the striatum of both control rats and wild-type, mice suggesting the presence of at least two α6β2* nAChRs. In rats receiving nicotine, competition analysis of the data also yielded a biphasic curve; however, there was a preferential decrease in the f1 fraction (f1:f2 = 26:74). In contrast, E11A competition analyses using striatum of non-nicotine-treated α4 nAChR-null mutant mice yielded monophasic curves, suggesting a loss in the very-high-affinity binding site. Similar monophasic curves were obtained in mice (wild type and α4 nAChR-null mutants) receiving nicotine. Each value represents the mean ± S.E.M. of six to eight rats or three mice. The numbers in parentheses are the 95% confidence intervals (CI).

Species & Genotype Treatment Preferred Model (No. of Sites) E11A Ratio (IC502/IC501) Fraction of Receptors
IC501 (CI) IC502 (CI) f1 f2
pM %
Rat
N.A. Control Two 0.017 30 1765 51 49
(0.014-0.021) (25-35)
Nicotine Two 0.017 11 647 26 74
(0.009-0.034) (9.2-13.6)
Mouse
Wild type Control Two 0.011 6.5 590 34 66
(0.002-0.032) (4.3-9.7)
Nicotine One 2.3 100
(1.5-2.9)
α4(−/−) Control One 2.1 100
(1.3-3.9)
Nicotine One 1.1 100
(0.7-1.5)
  • N.A., not available.