Published online before print September 22, 2005, doi: 10.1161/01.RES.0000187474.47805.30
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 American Heart Association, Inc.
Cellular Biology |
Modulation of the Ca2 Permeable Cation Channel TRPV4 by Cytochrome P450 Epoxygenases in Vascular Endothelium
From the Department of Physiology (J.V., G.O., A.J., T.V., B.N.), Campus Gasthuisberg, KU Leuven, Belgium; Institut für Kardiovaskuläre Physiologie (B.F., I.F., R.B.), Johann Wolfgang Goethe-Universität Theodor-Stern Kai 7, Frankfurt am Main, Germany; Department of Entomology and UC Davis Cancer Center (C.M., B.D.H.), University of California, Davis; and Jichi Medical School (M.S.) Yakushiji, Kawachi, Tochigi, Japan.
Correspondence to B. Nilius, Katholieke Universiteit Leuven, Department of Physiology, Campus Gasthuisberg, O/N, Herestr 49, Leuven, B-3000, Belgium. E-mail bernd.nilius{at}med.kuleuven.ac.be
TRPV4 is a broadly expressed Ca2+-permeable cation channel in the vanilloid subfamily of transient receptor potential channels. TRPV4 gates in response to a large variety of stimuli, including cell swelling, warm temperatures, the synthetic phorbol ester 4
-phorbol 12,13-didecanoate (4-PDD), and the endogenous lipid arachidonic acid (AA). Activation by cell swelling and AA requires cytochrome P450 (CYP) epoxygenase activity to convert AA to epoxyeicosatrienoic acids (EETs) such as 5,6-EET, 8,9-EET, which both act as direct TRPV4 agonists. To evaluate the role of TRPV4 and its modulation by the CYP pathway in vascular endothelial cells, we performed Ca2+ imaging and patch-clamp measurements on mouse aortic endothelial cells (MAECs) isolated from wild-type and TRPV4–/– mice. All TRPV4-activating stimuli induced robust Ca2+ responses in wild-type MAECs but not in MAECs isolated from TRPV4–/– mice. Upregulation of CYP2C expression by preincubation with nifedipine enhanced the responses to AA and cell swelling in wild-type MAECs, whereas responses to other stimuli remained unaffected. Conversely, inhibition of CYP2C9 activity with sulfaphenazole abolished the responses to AA and hypotonic solution (HTS). Moreover, suppression of EET hydrolysis using 1-adamantyl-3-cyclo-hexylurea or indomethacin, inhibitors of soluble epoxide hydrolases (sEHs), and cyclooxygenases, respectively, enhanced the TRPV4-dependent responses to AA, HTS, and EETs but not those to 4-PDD or heat. Together, our data establish that CYP-derived EETs modulate the activity of TRPV4 channels in endothelial cells and shows the unraveling of novel modulatory pathways via CYP2C modulation and sEH inhibition.
Key Words: TRP channels • endothelium • epoxygenases • epoxide hydrolases
This article has been cited by other articles:
 |
|
 |
|
  A. E. Loot, R. Popp, B. Fisslthaler, J. Vriens, B. Nilius, and I. Fleming Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation Cardiovasc Res, August 27, 2008; (2008) cvn207v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Pla, C. Grange, S. Antoniotti, C. Tomatis, A. Merlino, B. Bussolati, and L. Munaron Arachidonic Acid-Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis Mol. Cancer Res., April 1, 2008; 6(4): 535 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-Y. Jian, J. A. King, A.-B. Al-Mehdi, W. Liedtke, and M. I. Townsley High Vascular Pressure-Induced Lung Injury Requires P450 Epoxygenase-Dependent Activation of TRPV4 Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 386 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D'hoedt, G. Owsianik, J. Prenen, M. P. Cuajungco, C. Grimm, S. Heller, T. Voets, and B. Nilius Stimulus-specific Modulation of the Cation Channel TRPV4 by PACSIN 3 J. Biol. Chem., March 7, 2008; 283(10): 6272 - 6280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Saliez, C. Bouzin, G. Rath, P. Ghisdal, F. Desjardins, R. Rezzani, L.F. Rodella, J. Vriens, B. Nilius, O. Feron, et al. Role of Caveolar Compartmentation in Endothelium-Derived Hyperpolarizing Factor-Mediated Relaxation: Ca2+ Signals and Gap Junction Function Are Regulated by Caveolin in Endothelial Cells Circulation, February 26, 2008; 117(8): 1065 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Fleming, A. Rueben, R. Popp, B. Fisslthaler, S. Schrodt, A. Sander, J. Haendeler, J. R. Falck, C. Morisseau, B. D. Hammock, et al. Epoxyeicosatrienoic Acids Regulate Trp Channel Dependent Ca2+ Signaling and Hyperpolarization in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2612 - 2618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Larsen, D. X. Zhang, and D. D. Gutterman Epoxyeicosatrienoic Acids, TRP Channels, and Intracellular Ca2+ in the Vasculature: An Endothelium-Derived Endothelium-Hyperpolarizing Factor? Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2496 - 2498. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wu, X. Gao, R. C. Brown, S. Heller, and R. G. O'Neil Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1699 - F1713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ke, Y.-F. Xiao, J. A. Bradbury, J. P. Graves, L. M. DeGraff, J. M. Seubert, and D. C. Zeldin Electrophysiological Properties of Cardiomyocytes Isolated from CYP2J2 Transgenic Mice Mol. Pharmacol., October 1, 2007; 72(4): 1063 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hamanaka, M.-Y. Jian, D. S. Weber, D. F. Alvarez, M. I. Townsley, A. B. Al-Mehdi, J. A. King, W. Liedtke, and J. C. Parker TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L923 - L932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chatterjee, S. Baeter, and J. Bhattacharya Endothelial and epithelial signaling in the lung Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L517 - L519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Reading and J. E. Brayden Central Role of TRPM4 Channels in Cerebral Blood Flow Regulation Stroke, August 1, 2007; 38(8): 2322 - 2328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vriens, G. Owsianik, A. Janssens, T. Voets, and B. Nilius Determinants of 4{alpha}-Phorbol Sensitivity in Transmembrane Domains 3 and 4 of the Cation Channel TRPV4 J. Biol. Chem., April 27, 2007; 282(17): 12796 - 12803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Spector and A. W. Norris Action of epoxyeicosatrienoic acids on cellular function Am J Physiol Cell Physiol, March 1, 2007; 292(3): C996 - C1012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Marrelli, R. G. O'Neil, R. C. Brown, and R. M. Bryan Jr. PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1390 - H1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mahieu, G. Owsianik, L. Verbert, A. Janssens, H. De Smedt, B. Nilius, and T. Voets TRPM8-independent Menthol-induced Ca2+ Release from Endoplasmic Reticulum and Golgi J. Biol. Chem., February 2, 2007; 282(5): 3325 - 3336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Alvarez, J. A. King, D. Weber, E. Addison, W. Liedtke, and M. I. Townsley Transient Receptor Potential Vanilloid 4-Mediated Disruption of the Alveolar Septal Barrier: A Novel Mechanism of Acute Lung Injury Circ. Res., October 27, 2006; 99(9): 988 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Inoue, L. J. Jensen, J. Shi, H. Morita, M. Nishida, A. Honda, and Y. Ito Transient Receptor Potential Channels in Cardiovascular Function and Disease Circ. Res., July 21, 2006; 99(2): 119 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, B. Bandyopadhyay, T. Nakamoto, B. Singh, W. Liedtke, J. E. Melvin, and I. Ambudkar A Role for AQP5 in Activation of TRPV4 by Hypotonicity: CONCERTED INVOLVEMENT OF AQP5 AND TRPV4 IN REGULATION OF CELL VOLUME RECOVERY J. Biol. Chem., June 2, 2006; 281(22): 15485 - 15495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Fleming and R. Busse Endothelium-Derived Epoxyeicosatrienoic Acids and Vascular Function Hypertension, April 1, 2006; 47(4): 629 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Arniges, J. M. Fernandez-Fernandez, N. Albrecht, M. Schaefer, and M. A. Valverde Human TRPV4 Channel Splice Variants Revealed a Key Role of Ankyrin Domains in Multimerization and Trafficking J. Biol. Chem., January 20, 2006; 281(3): 1580 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Kotlikoff EDHF Redux: EETs, TRPV4, and Ca2+ Sparks Circ. Res., December 9, 2005; 97(12): 1209 - 1210. [Full Text] [PDF]
|
|