| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Asthma Research Group, Firestone Institute for Respiratory Health, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
We investigated the mechanisms that underlie the responses to norepinephrine (NE) and thromboxane (Tx) A2 (TxA2) in the canine pulmonary vasculature with fura 2 fluorimetric, intracellular microelectrode, and force transduction techniques. KCl, caffeine, and cyclopiazonic acid elevated intracellular Ca2+ concentration levels and tone, indicating that Ca2+ mobilization is sufficient to produce contraction. However, contractions evoked by NE or the TxA2 mimetic U-46619 were unaffected by nifedipine or by omitting external Ca2+ and were reduced only partially by depleting the internal Ca2+ store; furthermore, NE-evoked depolarization was subthreshold for voltage-dependent Ca2+ currents. Agonist-evoked contractions were insensitive to inhibitors of protein kinase C (calphostin C and chelerythrine), mitogen-activated protein kinase kinase (PD-98059), and p38 kinase (SB-203580) but were abolished by the tyrosine kinase inhibitor genistein and the Rho kinase inhibitor Y-27632. We conclude that, although Ca2+ influx and Ca2+ release are sufficient for contraction, they are not necessary for adrenergic or TxA2 contractions. Instead, excitation-contraction coupling involves the activation of tyrosine kinase and Rho kinase, leading to enhanced Ca2+ sensitivity of the contractile apparatus.
mitogen-activated protein kinase; norepinephrine; thromboxane A2; intracellular calcium; protein kinase C; myosin light chain kinase; myosin light chain phosphatase
This article has been cited by other articles:
|
|
 |
|
  G. A. Knock, V. A. Snetkov, Y. Shaifta, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery Cardiovasc Res, December 1, 2008; 80(3): 453 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. M. Seok, I. Baek, Y.-H. Kim, Y.-S. Jeong, I.-J. Lee, D. H. Shin, Y. H. Hwang, and I. K. Kim Isoflavone Attenuates Vascular Contraction through Inhibition of the RhoA/Rho-Kinase Signaling Pathway J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 991 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lu, A. Alioua, Y. Kumar, P. Kundu, M. Eghbali, N. V. Weisstaub, J. A. Gingrich, E. Stefani, and L. Toro c-Src tyrosine kinase, a critical component for 5-HT2A receptor-mediated contraction in rat aorta J. Physiol., August 15, 2008; 586(16): 3855 - 3869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Knock, Y. Shaifta, V. A. Snetkov, B. Vowles, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery Cardiovasc Res, February 1, 2008; 77(3): 570 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ding and P. A. Murray The Differential Effects of Intravenous Anesthetics on Myofilament Ca2+ Sensitivity in Pulmonary Venous Smooth Muscle Anesth. Analg., November 1, 2007; 105(5): 1278 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, L. Weigand, J. Foxson, L. A. Shimoda, and J. T. Sylvester Ca2+ signaling in hypoxic pulmonary vasoconstriction: effects of myosin light chain and Rho kinase antagonists Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L674 - L685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Barman Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L472 - L479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Weigand, J. T. Sylvester, and L. A. Shimoda Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L284 - L290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ding and P. A. Murray Cellular mechanisms of thromboxane A2-mediated contraction in pulmonary veins Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L825 - L833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Losapio, R. S. Sprague, A. J. Lonigro, and A. H. Stephenson 5,6-EET-induced contraction of intralobar pulmonary arteries depends on the activation of Rho-kinase J Appl Physiol, October 1, 2005; 99(4): 1391 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cogolludo, L. Moreno, F. Lodi, J. Tamargo, and F. Perez-Vizcaino Postnatal maturational shift from PKC{zeta} and voltage-gated K+ channels to RhoA/Rho kinase in pulmonary vasoconstriction Cardiovasc Res, April 1, 2005; 66(1): 84 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagaoka, K. A. Fagan, S. A. Gebb, K. G. Morris, T. Suzuki, H. Shimokawa, I. F. McMurtry, and M. Oka Inhaled Rho Kinase Inhibitors Are Potent and Selective Vasodilators in Rat Pulmonary Hypertension Am. J. Respir. Crit. Care Med., March 1, 2005; 171(5): 494 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ding and P. A. Murray Regulation of pulmonary venous tone in response to muscarinic receptor activation Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L131 - L140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nagaoka, Y. Morio, N. Casanova, N. Bauer, S. Gebb, I. McMurtry, and M. Oka Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L665 - L672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Hyvelin, C. O'Connor, and P. McLoughlin Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L673 - L684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Martin, R. Goggel, A.-R. Ressmeyer, and S. Uhlig Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L250 - L257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bailly, A. J. Ridley, S. M. Hall, and S. G. Haworth RhoA Activation by Hypoxia in Pulmonary Arterial Smooth Muscle Cells Is Age and Site Specific Circ. Res., May 28, 2004; 94(10): 1383 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. SOMLYO and A. V. SOMLYO Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase Physiol Rev, October 1, 2003; 83(4): 1325 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Damron, N. Kanaya, Y. Homma, S.-O. Kim, and P. A. Murray Role of PKC, tyrosine kinases, and Rho kinase in alpha -adrenoreceptor-mediated PASM contraction Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1051 - L1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Karamsetty, J. R. Klinger, and N. S. Hill Evidence for the role of p38 MAP kinase in hypoxia-induced pulmonary vasoconstriction Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L859 - L866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Janssen Isoprostanes: an overview and putative roles in pulmonary pathophysiology Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1067 - L1082. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
