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Planta Med 2004; 70(2): 108-112
DOI: 10.1055/s-2004-815485
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Isosteviol as a Potassium Channel Opener to Lower Intracellular Calcium Concentrations in Cultured Aortic Smooth Muscle Cells

Kar-Lok Wong1 , 6 , Hung-Yu Yang2 , Paul Chan1 , 2 , Tz-Hurng Cheng2 , Ju-Chi Liu1 , 2 , Feng-Lin Hsu3 , I-Min Liu4 , Yu-Wan Cheng5 , Juei-Tang Cheng5
  • 1Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, R.O.C.
  • 2Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan, R.O.C.
  • 3Graduate School of Pharmacology, Taipei Medical University, Taipei, Taiwan, R.O.C.
  • 4Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung Province, Taiwan, R.O.C.
  • 5Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
  • 6Department of Anesthesia, China Medical University Hospital, Taichung, Taiwan, R.O.C.
The present study was supported in part by a grant from the National Science Council (NSC89-2320-B006-009), and a grant from Taipei Mackay Memorial Hospital Grant No. 9029#
Further Information

Publication History

Received: July 7, 2003

Accepted: November 8, 2003

Publication Date:
02 March 2004 (online)

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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 [Ca2+]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 Ca2+-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.

Key words

Isosteviol - intracellular calcium concentrations - A7r5 cells - ATP-sensitive potassium channel - small conductance calcium-activated potassium channel - voltage-gated channel - Stevia rebaudiana - Compositae

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Paul Chan, MD PhD, FCP, FACC, FRCP (Lon.)

Division of Cardiovascular Medicine

Taipei Medical University-Wan Fang Hospital

No.111, Hsing Lung Road, Section 3

Wen Shan District

Taipei

Taiwan 117

Republic of China

Phone: +886-2-2930-7930 ext.2816, 2817

Fax: +886-2-2933-9378

Email: chanpaul@wanfang.gov.tw