Dk. Miller et al., Lobeline inhibits nicotine-evoked [H-3]dopamine overflow from rat striatalslices and nicotine-evoked Rb-86(+) efflux from thalamic synaptosomes, NEUROPHARM, 39(13), 2000, pp. 2654-2662
The present study evaluated the interaction of lobeline with neuronal nicot
inic acetylcholine receptors using two in vitro assays, [H-3] overflow from
[H-3]dopamine ([H-3]DA)-preloaded rat striatal slices and Rb-86(+) efflux
from rat thalamic synaptosomes. To assess agonist interactions, the effect
of lobeline was determined and compared to S(-)-nicotine. To assess antagon
ist interactions, the ability of lobeline to inhibit the effect of S(-)-nic
otine was determined. Both S(-)-nicotine (0.1-1 muM) and lobeline (>1.0 muM
) evoked [H-3] overflow from superfused [H-3]DA-preloaded striatal slices.
However, lobeline-evoked [H-3] overflow is mecamylamine-insensitive, indica
ting that this response is not mediated by nicotinic receptors. Moreover, a
t concentrations (<1.0 <mu>M) which did not evoke [H-3] overflow, lobeline
inhibited S(-)-nicotine (0.1-10 muM)-evoked [H-3] overflow, shifting the S(
-)-nicotine concentration-response curve to the right. S(-)-Nicotine (30 nM
-300 muM) increased (EC50 value=0.2 muM) Rb-86(+) efflux from thalamic syna
ptosomes. In contrast, lobeline (1 nM-10 muM) did not evoke Rb-86+ efflux,
and the lack of intrinsic activity indicates that lobeline is not an agonis
t at this nicotinic receptor subtype. Lobeline completely inhibited (IC50 v
alue=0.7 muM) Rb-86(+) efflux evoked by 1 muM S(-)-nicotine, a concentratio
n which maximally stimulated Rb-86(+) efflux. Thus, the results of these in
vitro experiments demonstrate that lobeline inhibits the effects of S(-)-n
icotine, and suggest that lobeline acts as a nicotinic receptor antagonist.
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