Biomolecules & Therapeutics

  • 제19권4호
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  • Pages.460-465
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  • 2011
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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DOI QR코드

DOI QR Code

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

  • Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Jeong, Ji-Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • La, Hyen-Oh (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
  • 투고 : 2011.04.26
  • 심사 : 2011.07.06
  • 발행 : 2011.10.30
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초록

The present study was undertaken to investigate the influence of quercetin 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. Quercetin at a low concentration (0.01-0.03 mM) directly and more significantly relaxed fluoride or thromboxane $A_2$-induced vascular contraction than phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, quercetin more significantly inhibited thromboxane $A_2$-induced increases in pMYPT1 levels than phorbol ester-induced increases. It also more significantly inhibited thromboxane $A_2$-induced increases in pMYPT1 levels than 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 quercetin on agonist-induced vascular contraction regardless of endothelial function.

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참고문헌

  1. Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y. and Kaibuchi, K. (1996). Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. 271, 20246-20249. https://doi.org/10.1074/jbc.271.34.20246
  2. Bigay, J., Deterre, P., Pfi ster, C. and Chabre, M. (1985). Fluoroaluminates activate transducin-GDP by mimicking the gamma-phosphate of GTP in its binding site. FEBS Lett. 191, 181-185. https://doi.org/10.1016/0014-5793(85)80004-1
  3. Bischoff, S. C. (2008). Quercetin: potentials in the prevention and therapy of disease. Curr. Opin. Clin. Nutr. Metab. Care 11, 733-740. https://doi.org/10.1097/MCO.0b013e32831394b8
  4. Blackmore, P. F. and Exton, J. H. (1986). Studies on the hepatic calcium- mobilizing activity of aluminum fluoride and glucagon. Modulation by cAMP and phorbol myristate acetate. J. Biol. Chem. 261, 11056-11063.
  5. Boots, A. W., Haenen, G. R. and Bast, A. (2008). Health effects of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol. 585, 325-337. https://doi.org/10.1016/j.ejphar.2008.03.008
  6. Chabre, M. (1990). Aluminofl uoride and beryllofl uoride complexes: a new phosphate analogs in enzymology. Trends Biochem. Sci. 15, 6-10. https://doi.org/10.1016/0968-0004(90)90117-T
  7. Cockcroft, S. and Taylor, J. A. (1987). 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. 241, 409-414.
  8. Davis, M. J., Wu, X., Nurkiewicz, T. R., Kawasaki, J., Gui, P., Hill, M. A. and Wilson, E. (2001). Regulation of ion channels by protein tyrosine phosphorylation. Am. J. Physiol. 281, H1835-H1862.
  9. Deng, J. T., Van Lierop, J. E., Sutherland, C. and Walsh, M. P. (2001). Ca2+-independent smooth muscle contraction: a novel function for integrin-linked kinase. J. Biol. Chem. 276, 16365-16373. https://doi.org/10.1074/jbc.M011634200
  10. Gilman, A. G. (1984). Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase. J. Clin. Invest. 73, 1-4. https://doi.org/10.1172/JCI111179
  11. Guardia, T., Rotelli, A. E., Juarez, A. O. and Pelzer, L. E. (2001). Antiinfl ammatory properties of plant fl avonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco. 56, 683-687. https://doi.org/10.1016/S0014-827X(01)01111-9
  12. Hollman, P. C. and Katan, M. B. (1999). Health effects and bioavailability of dietary flavonols. Free Radic. Res. 31, 75-80. https://doi.org/10.1080/10715769900301351
  13. 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
  14. Kanaho, Y., Moss, J. and Vaughan, M. (1985). Mechanism of inhibition of transducin GTPase activity by fluoride and aluminum. J. Biol. Chem. 260, 11493-11497.
  15. Khoo, N. K., White, C. R., Pozzo-Miller, L., Zhou, F., Constance, C., Inoue, T., Patel, R. P. and Parks, D. A. (2010). Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels. Free Radic. Biol. Med. 49, 339-347. https://doi.org/10.1016/j.freeradbiomed.2010.04.022
  16. Kitazawa, T., Masuo, M. and Somlyo, A. P. (1991). Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc. Natl. Acad. Sci. USA 88, 9307-9310. https://doi.org/10.1073/pnas.88.20.9307
  17. Knekt, P., Kumpulainen, J., Järvinen, R., Rissanen, H., Heliövaara, M., Reunanen, A., Hakulinen, T. and Aromaa, A. (2002). Flavonoid intake and risk of chronic diseases. Am. J. Clin. Nutr. 76, 560-568.
  18. Lotito, S. B. and Frei, B. (2006). Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion molecule expression in human aortic endothelial cells. Structure-function relationships and activity after first pass metabolism. J. Biol. Chem. 281, 37102-37110. https://doi.org/10.1074/jbc.M606804200
  19. Low, A. M. (1996). Role of tyrosine kinase on $Ca2^+$ entry and refi lling of agonist-sensitive $Ca2^+$ stores in vascular smooth muscles. Can. J. Physiol. Pharmacol. 74, 298-304. https://doi.org/10.1139/y96-021
  20. Mamani-Matsuda, M., Kauss, T., Al-Kharrat, A., Rambert, J., Fawaz, F., Thiolat, D., Moynet, D., Coves, S., Malvy, D. and Mossalayi, M. D. (2006). Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage infl ammatory mediators. Biochem. Pharmacol. 72, 1304-1310. https://doi.org/10.1016/j.bcp.2006.08.001
  21. Muranyi, A., MacDonald, J. A., Deng, J. T., Wilson, D. P., Haystead, T. A., Wlash, M. P., Erdodi, F., Kiss, E., Wu, Y. and Hartshorne, D. J. (2002). Phosphorylation of the myosin phosphatase target subunit by integrin-linked kinase. Biochem. J. 366, 211-216.
  22. Naderi, G. A., Asgary, S., Sarraf-Zadegan, N. and Shirvany, H. (2003). Anti-oxidant effect of fl avonoids on the susceptibility of LDL oxidation. Mol. Cell Biochem. 246, 193-196. https://doi.org/10.1023/A:1023483223842
  23. Nicholson, S. K., Tucker, G. A. and Brameld, J. M. (2008). Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc. Nutr. Soc. 67, 42-47. https://doi.org/10.1017/S0029665108006009
  24. Pfitzer, G. (2001). Invited reviews: regulation of myosin light chain phosphorylation in smooth muscle. J. Appl. Physiol. 91, 497-503.
  25. Ross, J. A. and Kasum, C. M. (2002). Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu. Rev. Nutr. 22, 19-34. https://doi.org/10.1146/annurev.nutr.22.111401.144957
  26. Rotelli, A. E., Guardia, T., Juarez, A. O., de la Rocha, N.E. and Pelzer, L. E. (2003). Comparative study of flavonoids in experimental models of infl ammation. Pharmacol. Res. 48, 601-606. https://doi.org/10.1016/S1043-6618(03)00225-1
  27. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. (2003). $Ca^{2+}$-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548-556. https://doi.org/10.1161/01.RES.0000090998.08629.60
  28. Shenolikar, S. and Nairn, A. C. (1991). Protein phosphatases: recent progress. Adv. Second Messenger Phosphoprotein Res. 23, 1-121.
  29. Shimizu, M. and Weinstein, I. B. (2005). Modulation of signal transduction by tea catechins and related phytochemicals. Mutat. Res. 591, 147-160. https://doi.org/10.1016/j.mrfmmm.2005.04.010
  30. Somlyo, A. P. and Somlyo, A. V. (1994). Signal transduction and regulation in smooth muscle. Nature 372, 231-236. https://doi.org/10.1038/372231a0
  31. Somlyo, A. P. and Somlyo, A. V. (1998). From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta. Physiol. Scand. 164, 437-448. https://doi.org/10.1046/j.1365-201X.1998.00454.x
  32. 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. 522, 177-185. https://doi.org/10.1111/j.1469-7793.2000.t01-2-00177.x
  33. 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
  34. Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. (1997). Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990-994. https://doi.org/10.1038/40187
  35. Wier, W. G. and Morgan, K. G. (2003). $\alpha$1-Adrenergic signaling mechanisms in contraction of resistance arteries. Rev. Physiol. Biochem. Pharmacol. 150, 91-139.
  36. 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 kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763-774. https://doi.org/10.1042/BJ20050237
  37. 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
  38. Zang, M., Xu, S., Maitland-Toolan, K. A., Zuccollo, A., Hou, X., Jiang, B., Wierzbicki, M., Verbeuren, T. J. and Cohen, R. A. (2006). Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 55, 2180-2191. https://doi.org/10.2337/db05-1188
  39. Zeng, Y. Y., Benishin, C. G. and Pang, P. K. (1989). Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies with fluoride. J. Pharmacol. Exp. Ther. 250, 343-351.

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