Planta Med 2003; 69(2): 118-124
DOI: 10.1055/s-2003-37711
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

The Mechanism of Inhibitory Actions of S-Petasin, a Sesquiterpene of Petasites formosanus, on L-Type Calcium Current in NG108-15 Neuronal Cells

Sheng-Nan Wu1, 2 , Hsinyo Chen3 , Yun-Lian Lin3
  • 1Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, R.O.C.
  • 2Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung City, Taiwan, R.O.C.
  • 3National Institute of Chinese Medicine, Taipei City, Taiwan, R.O.C.
Further Information

Publication History

Received: June 25, 2002

Accepted: October 3, 2002

Publication Date:
07 March 2003 (online)

Abstract

The effects of S-petasin, a sesquiterpene isolated from Petasites formosanus Kitamura, on ion currents in a mouse neuroblastoma and a rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. S-Petasin (1 - 300 μM) caused a decrease in the amplitude of L-type Ca2+ current (I Ca,L) in a concentration-dependent manner, however, it did not change the overall shape of the current-voltage relationship of I Ca,L. The IC50 value for S-petasin-induced inhibition of I Ca,L was 11 μM. S-Petasin (10 μM) shifted the steady-state inactivation of I Ca,L to a more negative membrane potential by approximately -10 mV. S-petasin could prolong the recovery of I Ca,L inactivation. The inhibitory effect of S-petasin on I Ca,L was found to exhibit tonic and use-dependent characteristics. S-Petasin could inhibit I Ca,L evoked by action potential waveforms effectively. S-Petasin also suppressed low voltage-activated I Ca,L in NG108-15 cells. S-Petasin at a concentration of 100 μM had little effect on voltage-dependent Na+ current; however, it did produce an inhibitory effect on delayed rectifier K+ current in a time-dependent manner. These results demonstrate that S-petasin can interact directly with L-type Ca2+ channels in NG108-15 cells. These effects could contribute to the regulation of neuronal activity if similar results were found in neurons in vivo.

Abbreviations

ICa,L:Voltage-dependent L-type Ca2+ current

IK(DR):Delayed rectifier K+ current

INa:Voltage-dependent Na+ current

I-V:Current-voltage

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, Roder T, Bestmann H J, Brune K. Identification and characterization of inhibitors of peptido-leukotriene synthesis from Petasite hybridus .  Planta Medica. 1994;  60 318-22
  • 3 Grossmann M, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine.  International Journal of Clinical Pharmacology and Therapeutics. 2000;  38 430-5
  • 4 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
  • 5 Lin H, Chien C H, Lin Y L, Chen C F, Wang P S. Inhibition of testosterone secretion by S-petasin in rat testicular interstitial cells.  Chinese Journal of Physiology. 2000;  43 99-103
  • 6 Thomet O A, Wiesmann U N, Blaster K, Simon H U. Differential inhibition of inflammatory effector functions by petasin, isopetasin and neopetasin in human eosinophils.  Clinical and Experimental Allergy. 2001;  31 1310-20
  • 7 Thomet O A, Wiesmann U N, Schapowal A, Bizer C, Simon H. Role of petasin in the potential anti-inflammatory activity of a plant extract of Petasite hybridus .  Biochemical Pharmacology. 2001;  61 041-7
  • 8 Ko W C, Lei C B, Lin Y L, Chen C F. Relaxing effects of petasins in guinea-pig trachea and their structure-activity relationships.  Planta Medica. 2000;  66 650-2
  • 9 Ko W C, Lei C B, Lin Y L, Chen C F. Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea.  Planta Medica. 2001;  67 224-9
  • 10 Wang G J, Shum A YC, Lin Y L, Liao J F, Wu X C, Ren J, Chen C F. Calcium channel blockade in vascular smooth muscle cells: major hypotensive mechanism of S-petasin, a hypotensive sesquiterpene from Petasites formosanus .  Journal of Pharmacology and Experimental Therapeutics. 2001;  297 240-8
  • 11 Wu S N, Lo Y K, Chen C C, Li H F, Chiang H T. Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells.  Biochemical Pharmacology. 2002;  63 199-206
  • 12 Striessnig J. Pharmacology, structure and function of cardiac L-type Ca2+ channels.  Cellular Physiology and Biochemistry. 1999;  9 242-69
  • 13 Hell J W, Westenbroek R E, Warner C, Ahlijanian M K, Prystay W, Gilbert M M, Snutch T P, Catterall W A. Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits.  Journal of Cell Biology. 1993;  123 949-62
  • 14 Kamp T J, Mitas M, Fields K L, Asoh S, Chin H, Marban E, Nirenberg M. Transcriptional regulation of the neuronal L-type calcium channel alpha 1D subunit gene.  Cellular and Molecular Neurobiology. 1995;  15 307-26
  • 15 Wu S N, Lo Y K, Chen H, Li H F, Chiang H T. Rutaecarpine-induced block of delayed rectifier K+ current in NG108-15 neuronal cells.  Neuropharmacology. 2001;  41 834-45
  • 16 Lo Y K, Wu S N, Lee C T, Li H F, Chiang H T. Characterization of action potential waveform-evoked L-type calcium currents in pituitary GH3 cells.  Pflügers Archiv. 2001;  442 547-57
  • 17 Xu W, Lipscombe D. Neuronal Cav1.3α1 L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.  Journal of Neuroscience. 2001;  21 5944-51
  • 18 Williams M E, Feldman D H, McCue A F, Brenner R, Velicelebi G, Ellis S B, Harpold M M. Structure and functional expression of alpha1, alpha2, and beta subunits of a novel human neuronal calcium channel subtype.  Neuron. 1992;  8 71-84
  • 19 Pancrazio J J, Viglione M P, Kleiman R J, Kim Y I. Verapamil-induced blockade of voltage-activated K+ current in small-cell lung cancer cells.  Journal of Pharmacology and Experimental Therapeutics. 1991;  257 184-91
  • 20 Trequattrini C, Catacuzzeno L, Petris A, Franciolini F. Verapamil block of the delayed rectifier K+ current in chick embryo dorsal root ganglion neurons.  Pflügers Archiv. 1998;  435 503-10

Dr. Sheng-Nan Wu

Department of Medical Education and Research

Kaohsiung Veterans General Hospital

No. 386, Ta-Chung 1st Road

Kaohsiung City 813

Taiwan

Republic of China

Email: snwu@isca.vghks.gov.tw

Phone: +886-7-3422121-1507

Fax: +886-7-3468056