Differential effects of quercetin, a natural polyphenolic flavonoid, on L-type calcium current in pituitary tumor (GH3) cells and neuronal NG108-15 cells.

The effects of quercetin, a natural polyphenolic compound, on voltage-dependent L-type Ca 2 + current (I C a ,L) in rat pituitary GH 3 cells were investigated with the aid of the whole-cell voltage-camp technique. Quercetin (0.5-200 pM) stimulated I C a , l l. in a concentration-dependent manner. The current-voltage (/-V) relationship of I C a , L was slightly shifted to more negative potentials in the presence of quercetin. The EC 5 0 value of the quercetin-induced stimulation of I C a , L was about 7 μM. The presence of quercetin (5 μM) shifted the steady state inactivation curve of I C a , L to a more negative potential by approximately -10 mV. Although quercetin might increase intracellular cyclic AMP, sp-cAMPS did not affect I C a , L . In addition, neither flavone nor wortmannin had any effect on the amplitude of I C a , L , while epicatechin and genistein slightly suppressed it. Quercetin (50 μM) decreased the amplitude of tetrodotoxin-sensitive Na current in GH 3 cells. Under current-clamp configuration, quercetin could increase the firing frequency of actions potentials. Conversely, in NG108-15 neuronal cells, quercetin suppressed the amplitude of I C a , L . The quercetin-induced inhibition of ICa,L was abolished in NG108-15 cells preincubated with t-butyl hydroperoxide (1 mM). Quercetin-mediated stimulation of I C a , L in GH 3 cells was presumably not associated with the level of intracellular cyclic AMP, or with the activity of tyrosine or phosphoinositide 3-kinases. Therefore, the effects of quercetin on ion currents may, at least in part, contribute to the underlying mechanisms through which it affects neuronal or neuroendocrine function.