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Differential effects of quercetin, a natural polyphenolic flavonoid, on L‐Type calcium current in pituitary tumor (GH 3 ) cells and neuronal NG108‐15 cells
Author(s) -
Wu ShengNan,
Chiang HungTing,
Shen AiYu,
Lo YukKeung
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10244
Subject(s) - quercetin , stimulation , chemistry , genistein , intracellular , flavonoid , biophysics , wortmannin , biochemistry , endocrinology , phosphorylation , biology , phosphatidylinositol , antioxidant
Abstract The effects of quercetin, a natural polyphenolic compound, on voltage‐dependent L‐type Ca 2+ current ( I Ca,L ) in rat pituitary GH 3 cells were investigated with the aid of the whole‐cell voltage‐camp technique. Quercetin (0.5–200 μM) stimulated I Ca,L in a concentration‐dependent manner. The current–voltage ( I–V ) relationship of I Ca,L was slightly shifted to more negative potentials in the presence of quercetin. The EC 50 value of the quercetin‐induced stimulation of I Ca,L was about 7 μM. The presence of quercetin (5 μM) shifted the steady state inactivation curve of I Ca,L to a more negative potential by approximately −10 mV. Although quercetin might increase intracellular cyclic AMP, sp‐cAMPS did not affect I Ca,L . In addition, neither flavone nor wortmannin had any effect on the amplitude of I Ca,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 Ca,L . The quercetin‐induced inhibition of I Ca,L was abolished in NG108‐15 cells preincubated with t ‐butyl hydroperoxide (1 mM). Quercetin‐mediated stimulation of I Ca,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. © 2003 Wiley‐Liss, Inc.