Calcium-antagonizing activity of S-petasin, a hypotensive sesquiterpene from Petasites formosanus, on inotropic and chronotropic responses in isolated rat atria and cardiac myocytes

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• 作者：Guei-Jane Wang ; Jyh-Fei Liao ; KadonK. Hintz ; Wen-Pin Chen ; Ming-Jai Su ; Yun-Lian Lin ; Chuen-Chao Shi ; Chieh-Fu Chen and Jun Ren
• 关键词：S ; petasin ; Heart rate ; Isolated atria ; Ventricular myocytes ; Intracellular Ca2+ transient ; ICa ; L
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2004
• 出版时间：March 2004
• 年：2004
• 卷：369
• 期：3
• 页码：322-329
• 全文大小：657 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Neurosciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1912

文摘

Petasites formosanus, an indigenous species of Petasites, has been used to treat cardiovascular diseases such as hypertension for years. We have suggested recently that S-petasin, a major sesquiterpene from P. formosanus, inhibits vascular smooth muscle contraction through inhibition of voltage-dependent Ca2+ channels, a phenomenon possibly responsible for the hypotensive effect of P. formosanus. This study was designed to examine the chronotropic and inotropic actions of S-petasin in the heart in vivo and in vitro. Administration of S-petasin (0.1–1.5 mg/kg i.v.) in anesthetized rats reduced heart rate dose-dependently. This response was consistent with significant suppression of both contractile amplitude and spontaneous firing rate of isolated atria, responses that were not antagonized by atropine (1 µM). Mechanical evaluation in isolated ventricular myocytes showed that S-petasin (0.1 to 100 µM) depressed peak myocyte contraction and intracellular Ca2+ transients concentration-dependently. The duration of myocyte contraction was not affected. Whole-cell voltage clamp analysis revealed that S-petasin inhibited the L-type Ca2+ current (I_Ca,L) concentration-dependently and shifted the steady-state inactivation curve of I_Ca,L to more negative potentials. However, a receptor-binding assay failed to identify any significant interaction between S-petasin (0.1–300 µM) and the dihydropyridine binding sites of L-type voltage-dependent Ca2+ channels. Taken together, these data show that the negative chronotropic and inotropic properties of S-petasin that can be ascribed mainly to I_Ca,L inhibition, but not to blockade of dihydropyridine binding sites of L-type Ca2+ channel or to muscarinic receptor activation.