Exocytosis elicited by ACh was increased by varenicline,
nicotine and by both drugs together in rat chromaffin cells treated
chronically with nicotine
In a different set of experiments, chromaffin cells from six rats were
incubated with 110 nM nicotine for 24 hours and then perfused during the
whole experiment. The same protocol as in Fig. 1 was performed.
Representative original Cm traces are drawn in Fig. 4A-D
for control conditions, and in the presence of varenicline, nicotine and
both drugs applied together, respectively. The exocytosis achieved in
control cells amounted to 58.2 ± 6.1 fF (n=8). Varenicline alone evoked
120.7 ± 20.7 fF (n=6, *p) and nicotine triggered 160.9 ± 28.5 fF (n=6,
*p). Varenicline and nicotine elicited 186.5 ± 32.3 fF (n=8, *p). The
average values of Cm are displayed in Fig. 4E and the
normalized values with respect to its own control are shown in Fig. 4F.
Varenicline alone exhibited an increase in the exocytotic value of 2.4 ±
0.5 fold (n=6; *p), and nicotine triggered 3.1 ± 0.6 fold more
exocytosis with respect to control (n=6; *p). The response elicited by
varenicline together with nicotine was 3.4 ± 0.7 fold with respect to
the control response (n=8; *p). Thus, exocytotic responses were also
increased by varenicline alone or in the presence of nicotine, when the
chronic nicotine treatment was applied.
The values achieved for the membrane potential in these cells were -62.2
±1.3 mV (n=8), -57.8 ± 7.5 mV (n=6), -55.2 ± 3.4 mV (n=6) and -51.5 ±
2.6 mV (n=8, *p), for control conditions, varenicline and nicotine
alone, and both drugs perfused together, respectively. This reflects
that nicotine, in the acute and chronic treatment, may depolarize the
cell membrane in the presence of varenicline.