Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells

Kar L. Wong, Hung Y. Yang, Paul Chan, Tzu-Hurng Cheng, Ju C. Liu, Feng-Lin Hsu, I. M. Liu, Yu W. Cheng, Juei Tang Cheng

Research output: Contribution to journalArticle

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Abstract

Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, and is commonly used as a non-caloric sugar substitute in Japan and Brazil. The present study attempted to elucidate the role of potassium (K +) channels in the action of isosteviol on intracellular calcium concentrations ([Ca2+]i) in cultured vascular smooth muscle (A7r5) cells using the Ca2+-sensitive dye Fura-2 as an indicator. The increase of [Ca2+]i in A7r5 cells produced by vasopressin (1 μmol/L) or phenylephrine (1 μmol/L) was attenuated by isosteviol from 0. 01 μmol/L to 10 μmol/L. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca2+]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca2+]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present. Therefore, not only did the ATP-sensitive potassium (KATP) channel affect the action of isosteviol on [Ca 2+]i modulation in A7r5 cells, but also those on the small conductance calcium-activated potassium (SKCa) channels and voltage-gated (Kv) channels. However, the blockers of large-conductance Ca 2+-activated potassium channels failed to modify the inhibitory action of isosteviol on [Ca2+]i. The obtained results indicated that a decrease of [Ca2+]i in A7r5 cells by isosteviol is mainly mediated by the selective opening of KATP channel or/and SKCa channel. Alteration in the Kv channel also plays a critical role in the inhibitory action of isosteviol.

Original languageEnglish
Pages (from-to)108-112
Number of pages5
JournalPlanta Medica
Volume70
Issue number2
DOIs
Publication statusPublished - Feb 2004

Fingerprint

Potassium Channels
potassium channels
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
Cells
Calcium
calcium
KATP Channels
4-aminopyridine
Apamin
glibenclamide
4-Aminopyridine
phenylephrine
vasopressin
Glyburide
Phenylephrine
Vasopressins
Small-Conductance Calcium-Activated Potassium Channels

Keywords

  • A7r5 cells
  • ATP-sensitive potassium channel
  • Compositae
  • Intracellular calcium concentrations
  • Isosteviol
  • Small conductance calcium-activated potassium channel
  • Stevia rebaudiana
  • Voltage-gated channel

ASJC Scopus subject areas

  • Plant Science
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. / Wong, Kar L.; Yang, Hung Y.; Chan, Paul; Cheng, Tzu-Hurng; Liu, Ju C.; Hsu, Feng-Lin; Liu, I. M.; Cheng, Yu W.; Cheng, Juei Tang.

In: Planta Medica, Vol. 70, No. 2, 02.2004, p. 108-112.

Research output: Contribution to journalArticle

Wong, Kar L. ; Yang, Hung Y. ; Chan, Paul ; Cheng, Tzu-Hurng ; Liu, Ju C. ; Hsu, Feng-Lin ; Liu, I. M. ; Cheng, Yu W. ; Cheng, Juei Tang. / Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. In: Planta Medica. 2004 ; Vol. 70, No. 2. pp. 108-112.
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AU - Wong, Kar L.

AU - Yang, Hung Y.

AU - Chan, Paul

AU - Cheng, Tzu-Hurng

AU - Liu, Ju C.

AU - Hsu, Feng-Lin

AU - Liu, I. M.

AU - Cheng, Yu W.

AU - Cheng, Juei Tang

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N2 - Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, and is commonly used as a non-caloric sugar substitute in Japan and Brazil. The present study attempted to elucidate the role of potassium (K +) channels in the action of isosteviol on intracellular calcium concentrations ([Ca2+]i) in cultured vascular smooth muscle (A7r5) cells using the Ca2+-sensitive dye Fura-2 as an indicator. The increase of [Ca2+]i in A7r5 cells produced by vasopressin (1 μmol/L) or phenylephrine (1 μmol/L) was attenuated by isosteviol from 0. 01 μmol/L to 10 μmol/L. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca2+]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca2+]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present. Therefore, not only did the ATP-sensitive potassium (KATP) channel affect the action of isosteviol on [Ca 2+]i modulation in A7r5 cells, but also those on the small conductance calcium-activated potassium (SKCa) channels and voltage-gated (Kv) channels. However, the blockers of large-conductance Ca 2+-activated potassium channels failed to modify the inhibitory action of isosteviol on [Ca2+]i. The obtained results indicated that a decrease of [Ca2+]i in A7r5 cells by isosteviol is mainly mediated by the selective opening of KATP channel or/and SKCa channel. Alteration in the Kv channel also plays a critical role in the inhibitory action of isosteviol.

AB - Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, and is commonly used as a non-caloric sugar substitute in Japan and Brazil. The present study attempted to elucidate the role of potassium (K +) channels in the action of isosteviol on intracellular calcium concentrations ([Ca2+]i) in cultured vascular smooth muscle (A7r5) cells using the Ca2+-sensitive dye Fura-2 as an indicator. The increase of [Ca2+]i in A7r5 cells produced by vasopressin (1 μmol/L) or phenylephrine (1 μmol/L) was attenuated by isosteviol from 0. 01 μmol/L to 10 μmol/L. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca2+]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca2+]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present. Therefore, not only did the ATP-sensitive potassium (KATP) channel affect the action of isosteviol on [Ca 2+]i modulation in A7r5 cells, but also those on the small conductance calcium-activated potassium (SKCa) channels and voltage-gated (Kv) channels. However, the blockers of large-conductance Ca 2+-activated potassium channels failed to modify the inhibitory action of isosteviol on [Ca2+]i. The obtained results indicated that a decrease of [Ca2+]i in A7r5 cells by isosteviol is mainly mediated by the selective opening of KATP channel or/and SKCa channel. Alteration in the Kv channel also plays a critical role in the inhibitory action of isosteviol.

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