Browse > Article
http://dx.doi.org/10.4196/kjpp.2013.17.1.31

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)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.17, no.1, 2013 , pp. 31-36 More about this Journal
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
ERK1/2; Eupatilin; MYPT1; Rho-kinase; Vasodilation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Wier WG, Morgan KG. Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. Rev Physiol Biochem Pharmacol. 2003;150:91-139.
2 Kanaho Y, Moss J, Vaughan M. Mechanism of inhibition of transducin GTPase activity by fluoride and aluminum. J Biol Chem. 1985;260:11493-11497.
3 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.   DOI   ScienceOn
4 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.   DOI
5 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.
6 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.   DOI
7 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.   DOI   ScienceOn
8 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.   DOI   ScienceOn
9 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.
10 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.   DOI   ScienceOn
11 Chabre M. Aluminofluoride and beryllofluoride complexes: a new phosphate analogs in enzymology. Trends Biochem Sci. 1990;15:6-10.   DOI   ScienceOn
12 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.   DOI   ScienceOn
13 Shenolikar S, Nairn AC. Protein phosphatases: recent progress. Adv Second Messenger Phosphoprotein Res. 1991;23:1-121.
14 Tsai MH, Jiang MJ. Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers Arch. 2006;453:223-232.   DOI   ScienceOn
15 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.   DOI   ScienceOn
16 Pfitzer G. Invited review: regulation of myosin phosphorylation in smooth muscle. J Appl Physiol. 2001;91:497-503.   DOI
17 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.   DOI   ScienceOn
18 Kalemba D, Kusewicz D, Swiader K. Antimicrobial properties of the essential oil of Artemisia asiatica Nakai. Phytother Res. 2002;16:288-291.   DOI   ScienceOn
19 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.   DOI
20 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.   DOI   ScienceOn
21 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.   DOI   ScienceOn
22 Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature. 1994;372:231-236.   DOI   ScienceOn
23 Somlyo AP, Somlyo AV. From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiol Scand. 1998;164:437-448.   DOI   ScienceOn
24 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.   DOI   ScienceOn
25 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.   DOI   ScienceOn
26 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.   DOI   ScienceOn