| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Neurobiology, Schering-Plough Research Institute, Kennilworth, NJ, USA
* To whom correspondence should be addressed. E-mail: Yanlin.jia{at}spcorp.com.
Hypotonic stimulation induces airway constriction in normal and asthmatic airways. However, the osmolarity sensor in the airway has not been characterized. TRPV4 (also
known as VR-OAC, VRL-2, TRP12, OTRPC4), an osmotic sensitive cation channel in the transient receptor potential (TRP) channel family, was recently cloned. In the present study, we show that TRPV4 mRNA was expressed in cultured human airway smooth muscle cells as analyzed by RT-PCR. Hypotonic stimulation induced Ca2+ influx in
human airway smooth muscle cells in an osmolarity-dependent manner, consistent with the reported biological activity of TRPV4 in transfected cells. In cultured muscle cells,
4
-phorbol 12, 13-didecanoate (4-PDD), a TRPV4 ligand, increased intracellular Ca2+
level only when Ca2+ was present in the extracellular solution. The 4-PDD-induced Ca2+ response was inhibited by ruthenium red (1 µM), a known TRPV4 inhibitor, but not by
capsazepine (1 µM), a TRPV1 antagonist, indicating that 4-PDD-induced Ca2+ response
is mediated by TRPV4. Verapamil (10 µM), a L-type voltage gated Ca2+ channel inhibitor, had no effect on the 4-PDD-induced Ca2+ response, excluding the involvement of L-type Ca2+ channels. Furthermore, hypotonic stimulation elicited smooth muscle contraction through a mechanism dependent on membrane Ca2+ channels
in both isolated human and guinea pig airways. Hypotonicity-induced airway contraction was not inhibited by L-type Ca2+ channel inhibitor nifedipine (1 µM) or by TRPV1 inhibitor capsazepine (1 µM). We conclude that functional TRPV4 is expressed in human airway smooth muscle cells and may act as an osmolarity sensor in the airway.
This article has been cited by other articles:
|
|
 |
|
  K. S. Thorneloe, A. C. Sulpizio, Z. Lin, D. J. Figueroa, A. K. Clouse, G. P. McCafferty, T. P. Chendrimada, E. S. R. Lashinger, E. Gordon, L. Evans, et al. N-((1S)-1-{[4-((2S)-2-{[(2,4-Dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a Novel and Potent Transient Receptor Potential Vanilloid 4 Channel Agonist Induces Urinary Bladder Contraction and Hyperactivity: Part I J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 432 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baroffio, E. Crimi, and V. Brusasco Review: Airway smooth muscle as a model for new investigative drugs in asthma Therapeutic Advances in Respiratory Disease, June 1, 2008; 2(3): 129 - 139. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Ito, H. Kume, K. Naruse, M. Kondo, N. Takeda, S. Iwata, Y. Hasegawa, and M. Sokabe A Novel Ca2+ Influx Pathway Activated by Mechanical Stretch in Human Airway Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 407 - 413. [Abstract] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 M. Y. Kochukov, T. A. McNearney, Y. Fu, and K. N. Westlund Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes Am J Physiol Cell Physiol, September 1, 2006; 291(3): C424 - C432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, Y. Fu, W. Tian, and D. M. Cohen Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1103 - F1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. K. Sidhaye, A. D. Guler, K. S. Schweitzer, F. D'Alessio, M. J. Caterina, and L. S. King Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions PNAS, March 21, 2006; 103(12): 4747 - 4752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Earley, T. J. Heppner, M. T. Nelson, and J. E. Brayden TRPV4 Forms a Novel Ca2+ Signaling Complex With Ryanodine Receptors and BKCa Channels Circ. Res., December 9, 2005; 97(12): 1270 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Clapham, D. Julius, C. Montell, and G. Schultz International Union of Pharmacology. XLIX. Nomenclature and Structure-Function Relationships of Transient Receptor Potential Channels Pharmacol. Rev., December 1, 2005; 57(4): 427 - 450. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Nilius, T. Voets, and J. Peters TRP Channels in Disease Sci. Signal., August 2, 2005; 2005(295): re8 - re8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Beech, K. Muraki, and R. Flemming Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP J. Physiol., September 15, 2004; 559(3): 685 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Liedtke and S.A. Simon A possible role for TRPV4 receptors in asthma Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L269 - L271. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
