Planta Med 2003; 69(6): 557-558
DOI: 10.1055/s-2003-40638
Letter
© Georg Thieme Verlag Stuttgart · New York

Tetramethylpyrazine as Potassium Channel Opener to Lower Calcium Influx into Cultured Aortic Smooth Muscle Cells

Chin-Chuan Tsai1 , Tung-Yuan Lai1 , Wei-Chan Huang2 , Tzyylin Yang2 , I-Min Liu3 , Kar-Lok Wong4 , Paul Chan4 , Juei-Tang Cheng2
  • 1Department of Traditional Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical College, Taichung City, Taiwan
  • 2Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
  • 3Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung Shien, Taiwan
  • 4Division of Cardiovascular Medicine, Taipei Medical University and affiliated Taipei Wan-Fang Hospital, Taipei City, Taiwan
Further Information

Publication History

Received: October 11, 2002

Accepted: February 15, 2003

Publication Date:
16 July 2003 (online)

Abstract

In the present study, the effect of tetramethylpyrazine (TMP) on calcium (Ca2+) influx was investigated in cultured vascular smooth muscle (A7r5) cells using Fura-2 as an indicator. The increase of Ca2+ concentration in A7r5 cells produced by vasopressin or phenylephrine was attenuated by TMP from 0.01 μmol/L to 1 mmol/L. The decrease in the intracellular potassium concentration in A7r5 cells by TMP from 0.01 μmol/L to 10 μmol/L was characterized using PBFI/AM. Inhibitors specific to the small conductance calcium-activated potassium (SKCa) channel or the ATP-sensitive potassium (KATP) channel abolished the actions of TMP. The obtained results indicate that the decrease of Ca2+ influx into A7r5 cells by TMP is mainly mediated by the opening of potassium channels.

References

  • 1 Kosuqe T, Kamiya H. Discovery of a pyrazine in a natural product: tetramethylpyrazine from cultures of a strain of Bacillus subtilis .  Nature. 1962;  193 776-8
  • 2 Guo S K, Chen K J, Qian Z H, Weng W L, Qian M Y. Tetramethylpyrazine in treatment of cardiovascular and cerebrovascular disease.  Planta Med. 1983;  47 89
  • 3 Dai X Z, Bache R J. Coronary and systemic hemodynamic effects of tetramethylpyrazine in the dog.  J Cardiovasc Pharmacol. 1985;  7 841-9
  • 4 Wu C C, Chiou W F, Yen M H. A possible mechanism of action of tetramethylpyrazine on vascular smooth muscle in rat aorta.  Eur J Pharmacol. 1989;  169 189-95
  • 5 Kwan C Y. Plant-derived drugs acting on cellular Ca2+ mobilization in vascular smooth muscle: tetramethylpyrazine and tetrandrine.  Stem cells. 1994;  12 63-7
  • 6 Tsai C C, Lai T Y, Huang W C, Liu I M, Cheng J T. Inhibitory effects of potassium channel blockers on tetramethylpyrazine-induced relaxation of rat aortic strip in vitro .  Life Sci. 2002;  71 1321-30
  • 7 Sheu J R, Kan Y C, Hung W C, Ko W C, Yen M H. Mechanisms involved in the antiplatelet activity of tetramethylpyrazine in human platelets.  Thromb Res. 1997;  88 259-70
  • 8 Kasner S E, Ganz M B. Regulation of intracellular potassium in mesangial cells: a fluorescence analysis using the dye, PBFI.  Am J Physiol. 1992;  262 F462-7
  • 9 Pirotte B, Ouedraogo R, de Tullio P, Khelili S, Somers F, Boverie S, Dupont L, Fontaine J, Damas J, Lebrun P. 3-Alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to diazoxide and pinacidil as potassium channel openers acting on vascular smooth muscle cells: design, synthesis, and pharmacological evaluation.  J Med Chem. 2000;  43 1456-66
  • 10 Nelson M T, Quayle J M. Physiological roles and properties of potassium channels in arterial smooth muscle.  Am J Physiol. 1995;  268 C799-822
  • 11 Grynkiewicz G, Poenie M, Tsien R Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties.  J Biol Chem. 1985;  260 3440-50

Chin-Chuan Tsai, M.D., Ph. D.

School of Post-Baccalaureate Chinese Medicine

China Medical College

Taichung City

Taiwan 40401

Republic of China

Phone: +886-4-2205-3366 ext. 1019

Fax: +886-4-2207-2475

Email: tsaic@mail.cmc.edu.tw

    >