DOI QR코드

DOI QR Code

The Inhibitory Effect of Eupatilin on the Agonist-Induced Regulation of Vascular Contractility

  • Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Kim, Hyeong-Dong (Department of Physical Therapy, College of Health Science, Korea University) ;
  • Jeong, Ji Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University)
  • Received : 2012.10.18
  • Accepted : 2013.01.19
  • Published : 2013.02.28

Abstract

The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane $A_2$ or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.

Keywords

References

  1. Kalemba D, Kusewicz D, Swiader K. Antimicrobial properties of the essential oil of Artemisia asiatica Nakai. Phytother Res. 2002;16:288-291. https://doi.org/10.1002/ptr.856
  2. Song HJ, Shin CY, Oh TY, Sohn UD. The protective effect ofeupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK. J Ethnopharmacol. 2008;118:94-101. https://doi.org/10.1016/j.jep.2008.03.010
  3. Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature. 1994;372:231-236. https://doi.org/10.1038/372231a0
  4. Somlyo AP, Somlyo AV. From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiol Scand. 1998;164:437-448. https://doi.org/10.1046/j.1365-201X.1998.00454.x
  5. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389:990-994. https://doi.org/10.1038/40187
  6. Sakurada S, Takuwa N, Sugimoto N, Wang Y, Seto M, Sasaki Y, Takuwa Y. Ca2+-dependent activation of Rho and Rho kinasein membrane depolarization-induced and receptor stimulation- induced vascular smooth muscle contraction. Circ Res. 2003;93:548-556. https://doi.org/10.1161/01.RES.0000090998.08629.60
  7. Kitazawa T, Masuo M, Somlyo AP. G protein-mediated inhibition of myosin light-chain phosphatase invascular smooth muscle. Proc Natl Acad Sci USA. 1991;88:9307-9310. https://doi.org/10.1073/pnas.88.20.9307
  8. Wier WG, Morgan KG. Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. Rev Physiol Biochem Pharmacol. 2003;150:91-139.
  9. Kanaho Y, Moss J, Vaughan M. Mechanism of inhibition of transducin GTPase activity by fluoride and aluminum. J Biol Chem. 1985;260:11493-11497.
  10. Blackmore PF, Exton JH. Studies on the hepatic calciummobilizing activity of aluminum fluoride and glucagon. Modulation by cAMP and phorbol myristate acetate. J Biol Chem. 1986;261:11056-11063.
  11. Cockcroft S, Taylor JA. Fluoroaluminates mimic guanosine 5'-[gamma-thio]triphosphate in activating the polyphosphoinositide phosphodiesterase of hepatocyte membranes. Role for the guanine nucleotide regulatory protein Gp in signal transduction. Biochem J. 1987;241:409-414. https://doi.org/10.1042/bj2410409
  12. Jeon SB, Jin F, Kim JI, Kim SH, Suk K, Chae SC, Jun JE, Park WH, Kim IK. A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem Biophys Res Commun. 2006;343:27-33. https://doi.org/10.1016/j.bbrc.2006.02.120
  13. Wilson DP, Susnjar M, Kiss E, Sutherland C, Walsh MP. Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem J. 2005;389: 763-774. https://doi.org/10.1042/BJ20050237
  14. Wooldridge AA, MacDonald JA, Erdodi F, Ma C, Borman MA, Hartshorne DJ, Haystead TA. 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. 2004;279:34496-34504. https://doi.org/10.1074/jbc.M405957200
  15. Zeng YY, Benishin CG, Pang PK. Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies with fluoride. J Pharmacol Exp Ther. 1989;250:343-351.
  16. Chabre M. Aluminofluoride and beryllofluoride complexes: a new phosphate analogs in enzymology. Trends Biochem Sci. 1990;15:6-10. https://doi.org/10.1016/0968-0004(90)90117-T
  17. Bigay J, Deterre P, Pfister C, Chabre M. Fluoroaluminates activate transducin-GDP by mimicking the gamma-phosphate of GTP in its binding site. FEBS Lett. 1985;191:181-185. https://doi.org/10.1016/0014-5793(85)80004-1
  18. Shenolikar S, Nairn AC. Protein phosphatases: recent progress. Adv Second Messenger Phosphoprotein Res. 1991;23:1-121.
  19. Tsai MH, Jiang MJ. Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers Arch. 2006;453:223-232. https://doi.org/10.1007/s00424-006-0133-y
  20. Somlyo AP, Somlyo AV. Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol. 2000;522:177-185. https://doi.org/10.1111/j.1469-7793.2000.t01-2-00177.x
  21. Pfitzer G. Invited review: regulation of myosin phosphorylation in smooth muscle. J Appl Physiol. 2001;91:497-503. https://doi.org/10.1152/jappl.2001.91.1.497
  22. Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem. 1996;271:20246-20249. https://doi.org/10.1074/jbc.271.34.20246
  23. Davis MJ, Wu X, Nurkiewicz TR, Kawasaki J, Gui P, Hill MA, Wilson E. Regulation of ion channels by protein tyrosine phosphorylation. Am J Physiol Heart Circ Physiol. 2001;281: H1835-1862. https://doi.org/10.1152/ajpheart.2001.281.5.H1835
  24. Low AM. Role of tyrosine kinase on $Ca^{2+}$ entry and refilling of agonist-sensitive $Ca^{2+}$ stores in vascular smooth muscles. Can J Physiol Pharmacol. 1996;74:298-304. https://doi.org/10.1139/y96-021
  25. Deng JT, Van Lierop JE, Sutherland C, Walsh MP. $Ca^{2+}$-independent smooth muscle contraction. a novel function for integrin-linked kinase. J Biol Chem. 2001;276:16365-16373. https://doi.org/10.1074/jbc.M011634200
  26. Murányi A, MacDonald JA, Deng JT, Wilson DP, Haystead TA, Walsh MP, Erdodi F, Kiss E, Wu Y, Hartshorne DJ. Phosphorylation of the myosin phosphatase target subunit by integrin-linked kinase. Biochem J. 2002;366:211-216. https://doi.org/10.1042/bj20020401

Cited by

  1. Eupatilin: a natural pharmacologically active flavone compound with its wide range applications vol.22, pp.1, 2013, https://doi.org/10.1080/10286020.2018.1492565