Planta Med 2001; 67(3): 224-229
DOI: 10.1055/s-2001-11991
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Mechanisms of Relaxant Action of S-Petasin and S-Isopetasin, Sesquiterpenes of Petasites formosanus, in Isolated Guinea Pig Trachea

Wun-Chang Ko1,*, Chien-Bang Lei1 , Yun-Lian Lin2 , Chieh-Fu Chen2
  • 1 Graduate Institute of Medical Sciences, Taipei Medical College, Taipei, Taiwan, R.O.C.
  • 2 National Research Institute of Chinese Medicine, Taipei, Taiwan, R.O.C.
Further Information

Publication History

March 7, 2000

July 3, 2000

Publication Date:
31 December 2001 (online)

Abstract

We investigated the mechanisms of action of S-petasin and S-isopetasin, from Petasites formosanus Kitamura which is used as a folk medicine for treating hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin non-competitively inhibited cumulative histamine-, and carbachol-induced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a competitive manner. S-Petasin also non-competitively inhibited cumulative Ca2+-induced contractions in depolarized (K+, 60 mM; histamine, 100 μM; or carbachol, 10 μM) guinea-pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The nifedipine (10 μM)-remaining tension of carbachol (0.2 μM)-induced precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have other mechanisms of relaxant action. The relaxant effect of S-petasin or S-isopetasin was unaffected by the presence of propranolol (1 μM), 2′,5′-dideoxyadenosine (10 μM), methylene blue (25 μM), glibenclamide (10 μM), N ω-nitro-L-arginine (20 μM), or α-chymotrypsin (1 U/ml). However, S-petasin (100 - 300 μM), but not S-isopetasin, significantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above results reveal that the mechanisms of relaxant action of S-petasin and S-isopetasin may be primarily due to its non-specific antispasmodic and antimuscarinic effects, respectively.

Abbreviations

ROCCs:receptor-operated calcium channels

VDCCs:voltage dependent calcium channels

cAMP:adenosine 3′,5′-cyclic monophosphate

cGMP:guanosine 3′,5′-cyclic monophosphate

PDE:phosphodiesterase

IBMX:3-isobutyl-1-methylxanthine

References

  • 1 Brune K, Bickel D, Peskar B A. Gastro-protective effects by extracts of Petasites hybridus: the role of inhibition of peptido-leukotriene synthesis.  Planta Medica. 1993;  59 494-6
  • 2 Bickel D, Röder T, Bestmann H J, Brune K. Identification and characterization of inhibitors of peptido-leukotriene-synthesis from Petasites hybridus .  Planta Medica. 1994;  60 318-22
  • 3 Wildi E, Langer T, Schaffner W, Büter K B. Quantitative analysis of petasin and pyrrolizidine alkaloids in leaves and rhizomes of in situ grown Petasites hybridus plants.  Planta Medica. 1998;  64 264-7
  • 4 Sasaki S I. Taiwan Minkan Yakuyo Shokubustsu Shi (A Manual of the Medicine Plants of Formosa). Taipei; Kobun Kan 1924: Appendix p. 9
  • 5 Lin Y L, Mei C H, Huang S L, Kuo Y H. Four new sesquiterpenes from Petasites formosanus .  Journal of Natural Products. 1998;  61 887-90
  • 6 Lin Y L, Ou J C, Chen C F, Kuo Y H. Eremophilanes from Petasites formosanus Kitamura.  Chemical and Pharmaceutical Bulletin. 1998;  46 1807-9
  • 7 Ko W C, Lei C B, Lin Y L, Chen C F. Relaxant effects of petasins in guinea-pig trachea and their structure-activity relationships.  Planta Medica. 2000;  66 650-2
  • 8 Cook S J, Archer K, Martin A, Buchheit K H, Fozard J R, Müller T, Miller A J, Elliott K RF, Foster R W, Small R C. Further analysis of the mechanisms underlying the tracheal relaxant action of SCA40.  British Journal of Pharmacology. 1995;  114 143-51
  • 9 Ariëns E J, van Rossum J M. pDx, pAx and pD′x values in the analysis of pharmacodynamics.  Archives Internationales de Pharmacodynamie et de Therapie. 1957;  110 275-97
  • 10 van Rossum J M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters.  Archives Internationales de Pharmacodynamie et de Therapie. 1963;  143 299-330
  • 11 Ko W C, Kuo S W, Sheu J R, Lin C H, Tzeng S H, Chen C M. Relaxant action mechanisms of quercetin 3,3′,4′,5,7-pentamethyl ether in isolated guinea-pig trachea.  New Taipei Journal of Medicine. 1999;  1 98-106
  • 12 Hoffman B B, Lefkowitz R J. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, Molinoff PB, Rubbon RW, Gilman AG, editors Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill 1996: 199-248
  • 13 Johnson R A, Yeung S M, Stubner D, Bushfield M, Shoshani I. Cation and structural requirements for P site-mediated inhibition of adenylate cyclase.  Molecular Pharmacology. 1989;  35 681-8
  • 14 Sabouni M H, Cushing D J, Makujina S R, Mustafa S J. Inhibition of adenylate cyclase attenuates adenosine receptor-mediated relaxation in coronary artery.  Journal of Pharmacology and Experimental Therapeutics. 1991;  254 508-12
  • 15 Gruetter C A, Kodowitz P J, Ignarro L. Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerine, sodium nitrate and amyl nitrite.  Canadian Journal of Physiology and Pharmacology. 1981;  59 150-6
  • 16 Murray M A, Boyle J P, Small R C. Cromakalim-induced relaxation of guinea-pig isolated trachealis: Antagonism by glibenclamide and by phentolamine.  British Journal of Pharmacology. 1989;  98 856-74
  • 17 Allen S L, Boyle P, Cortljo J, Forster R W, Morgan G P, Small R C. Electrical and mechanical effects of BRL 34915 in guinea-pig isolated trachealis.  British Journal of Pharmacology. 1986;  89 395-405
  • 18 Ishii K, Chang B, Kerwin J F, Huang Z J, Murad F. N ω-Nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation.  European Journal of Pharmacology. 1990;  176 219-23
  • 19 Tsien R W. Calcium channels in excitable cell membranes.  Annual Review of Physiology. 1983;  45 341-58
  • 20 Westfall D P, Gerthoffer W T, Webb R C. Vasodilators and nitric oxide synthase. In: Brody TM, Larner J, Minneman KP, editors Mosby, St. Louis; 1998: 239-47
  • 21 Wang G J, Lin Y L, Hsu S Y, Chen C F. Effects of S-petasin, an antihypertensive sesquiterpene from Petasites formosanus, on intracellular Ca2+ in rat thoracic aorta.  FASEB Journal. 1998;  12 A95

Prof. Wun-Chang Ko

Graduate Institute of Medical Sciences

Taipei Medical College

250 Wu-Hsing St.

Taipei 110

Taiwan, R.O.C.

Email: wc_ko@tmc.edu.tw

Fax: +886-2-2377-7639