Effects of ginsenoside on G protein-coupled inwardly rectifying K+ channel activity expressed in Xenopus oocytes

Seok Choi, Jun Ho Lee, Yang In Kim, Man Jong Kang, Hyewon Rhim, Sang Mok Lee, Seung Yeol Nah

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish
Pages (from-to)83-92
Number of pages10
JournalEuropean Journal of Pharmacology
Volume468
Issue number2
DOIs
Publication statusPublished - 2003 May 9

Keywords

  • G protein-coupled inwardly rectifying
  • Ginseng
  • Ginsenoside
  • K channel
  • Protein kinase C
  • Xenopus oocyte

ASJC Scopus subject areas

  • Pharmacology

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