Effect of varenicline and nicotine as agonists on nicotinic
currents and evoked exocytosis and on the ACh-evoked currents in rat
chromaffin cells
In order to determine whether the increased exocytosis observed might be
due to the agonist effect of the drugs, they were applied in 500 ms
pulses in chromaffin cells obtained from six rats. Representative
original recordings of the currents elicited by each agonist are shown
in Fig. 5A. ACh triggered a current of 671.1 ± 127.3 pA (n=11), while
varenicline elicited currents that amounted to 316.8 ± 143.6 pA (n=11;
*p), nicotine to 70.5 ± 24.5 pA (n=9; *p), and varenicline in the
presence of nicotine to 81.5 ± 33.7 pA (n=9; *p) (Fig. 5B). Thus,
varenicline, nicotine and both drugs applied together evoked smaller
currents with respect to ACh. In order to diminish the variability among
data, values were normalized, being 0.1 ± 0.9 (*p), 0.4 ± 1.3 (*p) and
0.1 ± 0.02 (*p) fold with respect to the matched control condition for
each value in the presence of both drugs perfused together, and
varenicline and nicotine alone, respectively.
These currents elicited exocytosis as shown by the Cmrecordings of Fig. 5C. ACh evoked 121.3 ± 34 fF (n=11), varenicline
triggered 147.5 ± 51.1 fF (n=11), nicotine evoked 114 ± 46.6 fF (n=9)
and both together elicited 54.6 ± 20.2 fF (n=9) (Fig. 5D). These values
were normalized with respect to the corresponding matched control,
amounting to 1.5 ± 0.5 and 1 ± 0.1- fold for varenicline and nicotine
perfused separately, and 0.4 ± 0.2- fold (*p) for varenicline and
nicotine perfused together, respectively.
Finally, the ACh-elicited currents obtained from ten rats were recorded
while perfusing varenicline or/and nicotine. Drugs inhibited nicotinic
currents as shown in the representative recordings displayed in Fig. 5E.
ACh evoked a current of 1242 ± 141.7
pA (n=20), that was reduced to 653.7 ± 164.6 pA in the presence of
varenicline (n=13, *p), to 639.7 ± 131.6 pA with nicotine (n=18, *p) and
to 729.8 ± 127.4 pA when both drugs were applied together (n=19, *p)
(Fig. 5F). These values represented 0.6 ± 0.1 (*p), 0.5 ± 0.1 (*p) and
0.6 ± 0.1 (*p) fold with respect to their control matched currents,
respectively.