Abstract
Recently, we provided evidence that ginsenoside, the active component of Panax ginseng, uses the pertussis toxin-insensitive Gαq/11-phospholipase C-β3 signal transduction pathway to increase Ca2+-activated Cl- currents in the Xenopus oocyte. Other investigators have shown that stimulation of receptors linked to the Gαq-phospholipase C pathway inhibits the activity of G protein-coupled inwardly rectifying K+ (GIRK) channels. In the present study, we sought to determine whether ginsenoside influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocytes injected with GIRK 1/4 channel cRNA, bath-applied ginsenoside inhibited the high K+ solution-elicited GIRK current (EC50: 4.9±4.3 μg/ml). Pretreatment of the oocyte with pertussis toxin reduced the high K+ solution-elicited GIRK current by 49%, but it did not alter the inhibitory effect of ginsenoside on the GIRK current. Prior intraoocyte injection of cRNA(s) coding Gαq, Gα11 or Gαq/Gα11, but not Gαi2 or GαoA, attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding Gβ1γ2 also attenuated the ginsenoside effect. Preincubation of GIRK channel-expressing oocytes with phospholipase C inhibitor, {1-[6-((17b-3-Methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione} (U73122), or protein kinase C inhibitor, staurosporine or chelerythrine, blocked the inhibitory ginsenoside effect on the GIRK current. Intraoocyte injection of bis (o-aminophenoxy)ethane-N,N,N′,N′-tetracetic acid (BAPTA), a free Ca2+ chelator, had no significant effect on the action of ginsenoside. Taken together, these results suggest that ginsenoside inhibits the activity of the GIRK 1/4 channel expressed in the Xenopus oocyte through a pertussis toxin-insensitive and Gαq/11-, phospholipase C- and protein kinase C-mediated signal transduction pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 83-92 |
| Number of pages | 10 |
| Journal | European Journal of Pharmacology |
| Volume | 468 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2003 May 9 |
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Keywords
- G protein-coupled inwardly rectifying
- Ginseng
- Ginsenoside
- K channel
- Protein kinase C
- Xenopus oocyte
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Effects of ginsenoside on G protein-coupled inwardly rectifying K+ channel activity expressed in Xenopus oocytes. / Choi, Seok; Lee, Jun Ho; Kim, Yang In; Kang, Man Jong; Rhim, Hyewon; Lee, Sang Mok; Nah, Seung Yeol.
In: European Journal of Pharmacology, Vol. 468, No. 2, 09.05.2003, p. 83-92.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of ginsenoside on G protein-coupled inwardly rectifying K+ channel activity expressed in Xenopus oocytes
AU - Choi, Seok
AU - Lee, Jun Ho
AU - Kim, Yang In
AU - Kang, Man Jong
AU - Rhim, Hyewon
AU - Lee, Sang Mok
AU - Nah, Seung Yeol
PY - 2003/5/9
Y1 - 2003/5/9
N2 - Recently, we provided evidence that ginsenoside, the active component of Panax ginseng, uses the pertussis toxin-insensitive Gαq/11-phospholipase C-β3 signal transduction pathway to increase Ca2+-activated Cl- currents in the Xenopus oocyte. Other investigators have shown that stimulation of receptors linked to the Gαq-phospholipase C pathway inhibits the activity of G protein-coupled inwardly rectifying K+ (GIRK) channels. In the present study, we sought to determine whether ginsenoside influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocytes injected with GIRK 1/4 channel cRNA, bath-applied ginsenoside inhibited the high K+ solution-elicited GIRK current (EC50: 4.9±4.3 μg/ml). Pretreatment of the oocyte with pertussis toxin reduced the high K+ solution-elicited GIRK current by 49%, but it did not alter the inhibitory effect of ginsenoside on the GIRK current. Prior intraoocyte injection of cRNA(s) coding Gαq, Gα11 or Gαq/Gα11, but not Gαi2 or GαoA, attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding Gβ1γ2 also attenuated the ginsenoside effect. Preincubation of GIRK channel-expressing oocytes with phospholipase C inhibitor, {1-[6-((17b-3-Methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione} (U73122), or protein kinase C inhibitor, staurosporine or chelerythrine, blocked the inhibitory ginsenoside effect on the GIRK current. Intraoocyte injection of bis (o-aminophenoxy)ethane-N,N,N′,N′-tetracetic acid (BAPTA), a free Ca2+ chelator, had no significant effect on the action of ginsenoside. Taken together, these results suggest that ginsenoside inhibits the activity of the GIRK 1/4 channel expressed in the Xenopus oocyte through a pertussis toxin-insensitive and Gαq/11-, phospholipase C- and protein kinase C-mediated signal transduction pathway.
AB - Recently, we provided evidence that ginsenoside, the active component of Panax ginseng, uses the pertussis toxin-insensitive Gαq/11-phospholipase C-β3 signal transduction pathway to increase Ca2+-activated Cl- currents in the Xenopus oocyte. Other investigators have shown that stimulation of receptors linked to the Gαq-phospholipase C pathway inhibits the activity of G protein-coupled inwardly rectifying K+ (GIRK) channels. In the present study, we sought to determine whether ginsenoside influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocytes injected with GIRK 1/4 channel cRNA, bath-applied ginsenoside inhibited the high K+ solution-elicited GIRK current (EC50: 4.9±4.3 μg/ml). Pretreatment of the oocyte with pertussis toxin reduced the high K+ solution-elicited GIRK current by 49%, but it did not alter the inhibitory effect of ginsenoside on the GIRK current. Prior intraoocyte injection of cRNA(s) coding Gαq, Gα11 or Gαq/Gα11, but not Gαi2 or GαoA, attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding Gβ1γ2 also attenuated the ginsenoside effect. Preincubation of GIRK channel-expressing oocytes with phospholipase C inhibitor, {1-[6-((17b-3-Methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione} (U73122), or protein kinase C inhibitor, staurosporine or chelerythrine, blocked the inhibitory ginsenoside effect on the GIRK current. Intraoocyte injection of bis (o-aminophenoxy)ethane-N,N,N′,N′-tetracetic acid (BAPTA), a free Ca2+ chelator, had no significant effect on the action of ginsenoside. Taken together, these results suggest that ginsenoside inhibits the activity of the GIRK 1/4 channel expressed in the Xenopus oocyte through a pertussis toxin-insensitive and Gαq/11-, phospholipase C- and protein kinase C-mediated signal transduction pathway.
KW - G protein-coupled inwardly rectifying
KW - Ginseng
KW - Ginsenoside
KW - K channel
KW - Protein kinase C
KW - Xenopus oocyte
UR - http://www.scopus.com/inward/record.url?scp=0038058754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038058754&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(03)01666-2
DO - 10.1016/S0014-2999(03)01666-2
M3 - Article
C2 - 12742515
AN - SCOPUS:0038058754
VL - 468
SP - 83
EP - 92
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -