DOI QR코드

DOI QR Code

The Inhibitory Effect of Eupatilin on the Intestinal Contraction Induced by Carbachol

  • Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Lee, Jong-Min (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • La, Hyen-Oh (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
  • Received : 2010.07.27
  • Accepted : 2010.08.25
  • Published : 2010.10.31

Abstract

This study was conducted to determine whether treatment with the anti-inflammatory eupatilin influences intestinal smooth muscle contraction stimulated by carbachol and, if so, to investigate the related mechanism. Denuded ileal or colonic muscles from Sprague-Dawley rats were used for the study and measurements of isometric contractions were obtained using a computerized data acquisition system; this data was also combined with results from molecular experiments. Eupatilin from Artemisia asiatica Nakai significantly decreased carbachol-induced contractions in both ileal and colonic muscles. Interestingly, eupatilin decreased carbachol-induced phosphorylation of ERK1/2 more significantly than that of MYPT1 at Thr855 in ileal and colonic muscles. However, eupatilin significantly decreased phosphorylation of MYPT1 at Thr855, but only in ileal muscle. Therefore, thin filament regulation, including MEK inactivation and related phospho-ERK1/2 decrease, is mainly involved in the eupatilin-induced decrease of intestinal contraction induced by carbachol. In conclusion, this study provides the evidence and a possible related mechanism concerning the inhibitory effect of the flavonoid as an antispasmodic on the agonist-induced contractions in rat ileum and colonic muscles.

Keywords

References

  1. Caulfield, M. P. and Birdsall, N. J. M. (1998). International union of pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol. Rev. 50, 279-290.
  2. Ehlert, F. J. (2003). Contractile role of $M_2$ and $M_3$ muscarinic receptors in gastrointestinal, airway and urinary bladder smooth muscle. Life Sci. 74, 355-366. https://doi.org/10.1016/j.lfs.2003.09.023
  3. Gerthoffer, W. T. (2005). Signal-transduction pathways that regulate visceral smooth muscle function. III. Coupling of muscarinic receptors to signaling kinases and effector proteins in gastrointestinal smooth muscles. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G849-G853. https://doi.org/10.1152/ajpgi.00530.2004
  4. Jeon, S. B., Jin, F., Kim, J. I., Kim, S. H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H. and Kim I. K. (2006). A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem. Biophys. Res. Commun. 343, 27-33. https://doi.org/10.1016/j.bbrc.2006.02.120
  5. Kalemba, D., Kusewicz, D. and Swiader, K. (2002). Antimicrobial properties of the essential oil of Artemisia asiatica Nakai. Phytother. Res. 16, 288-291. https://doi.org/10.1002/ptr.856
  6. Murthy, K. S. (2006). Signaling for contraction and relaxation in smooth muscle of the gut. Annu. Rev. Physiol. 68, 345-374. https://doi.org/10.1146/annurev.physiol.68.040504.094707
  7. Mizuta, Y., Shikuwa, S., Isomoto, H., Mishima, R., Akazawa, Y., Masuda, J., Omagari, K., Takeshima, F. and Kohno, S. (2006). Recent insights into digestive motility in functional dyspepsia. J. Gastroenterol. 41, 1025-1040. https://doi.org/10.1007/s00535-006-1966-z
  8. Somlyo, A. P. and Somlyo, A. V. (2003). $Ca^{2+}$ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 83, 1325-1358. https://doi.org/10.1152/physrev.00023.2003
  9. Somlyo, A. P. and Somlyo, A. V. (2000). Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J. Physiol. (Lond.) 522, 177-185. https://doi.org/10.1111/j.1469-7793.2000.t01-2-00177.x
  10. Song, H. J., Shin, C. Y., Oh, T. Y. and Sohn, U. D. (2008). The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK. J. Ethnopharmacol. 118, 94-101. https://doi.org/10.1016/j.jep.2008.03.010
  11. Tsai, M. H. and Jiang, M. J. (2006). Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers. Arch. 453, 223-232. https://doi.org/10.1007/s00424-006-0133-y
  12. Unno, T., Matsuyama, H., Sakamoto, T., Uchiyama, M., Izumi, Y., Okamoto, H., Yamada, M., Wess, J. and Komori, S. (2005). $_2$ and $_3$ muscarinic receptor-mediated contractions in longitudinal smooth muscle of the ileum studied with receptor knockout mice. Br. J. Pharmacol. 146, 98-108. https://doi.org/10.1038/sj.bjp.0706300
  13. Webb, R. C. (2003). Smooth muscle contraction and relaxation. Adv. Physiol. Educ. 27, 201-206. https://doi.org/10.1152/advan.00025.2003
  14. Wilson, D. P., Susnjar, M., Kiss, E., Sutherland, C. and Walsh, M. P. (2005). Thromboxane $A_2$-induced contraction of rat caudal arterial smooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinasemediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763-774. https://doi.org/10.1042/BJ20050237
  15. Wooldridge, A. A., MacDonald, J. A., Erdodi, F., Ma, C., Borman, M. A., Hartshorne, D. J. and Haystead, T. A. (2004). Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J. Biol. Chem. 279, 34496-34504. https://doi.org/10.1074/jbc.M405957200

Cited by

  1. The neuroprotective effect of eupatilin against ischemia/reperfusion-induced delayed neuronal damage in mice vol.689, pp.1-3, 2012, https://doi.org/10.1016/j.ejphar.2012.05.042