Am J Physiol Cell Physiol Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 286: C1130-C1138, 2004; doi:10.1152/ajpcell.00429.2003
0363-6143/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (28)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhou, H.
Right arrow Articles by Murthy, K. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, H.
Right arrow Articles by Murthy, K. S.

RECEPTORS AND SIGNAL TRANSDUCTION

Distinctive G protein-dependent signaling in smooth muscle by sphingosine 1-phosphate receptors S1P1 and S1P2

Huiping Zhou and Karnam S. Murthy

Departments of Physiology and Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298

Submitted 6 October 2003 ; accepted in final form 28 December 2003

We examined expression of sphingosine 1-phosphate (S1P) receptors and sphingosine kinase (SPK) in gastric smooth muscle cells and characterized signaling pathways mediating S1P-induced 20-kDa myosin light chain (MLC20) phosphorylation and contraction. RT-PCR demonstrated expression of SPK1 and SPK2 and S1P1 and S1P2 receptors. S1P activated Gq, G13, and all Gi isoforms and stimulated PLC-{beta}1, PLC-{beta}3, and Rho kinase activities. PLC-{beta} activity was partially inhibited by pertussis toxin (PTX), G{beta} or G{alpha}q antibody, PLC-{beta}1 or PLC-{beta}3 antibody, and by expression of G{alpha}q or G{alpha}i minigene, and was abolished by a combination of antibodies or minigenes. S1P-stimulated Rho kinase activity was partially inhibited by expression of G{alpha}13 or G{alpha}q minigene and abolished by expression of both. S1P stimulated Ca2+ release that was inhibited by U-73122 and heparin and induced concentration-dependent contraction of smooth muscle cells (EC50 1 nM). Initial contraction and MLC20 phosphorylation were abolished by U-73122 and MLC kinase (MLCK) inhibitor ML-9. Initial contraction was also partially inhibited by PTX and G{alpha}q or G{beta} antibody and abolished by a combination of both antibodies. In contrast, sustained contraction and MLC20 phosphorylation were partially inhibited by a PKC or Rho kinase inhibitor (bisindolylmaleimide and Y-27632) and abolished by a combination of both inhibitors but not affected by U-73122 or ML-9. These results indicate that S1P induces 1) initial contraction mediated by S1P2 and S1P1 involving concurrent activation of PLC-{beta}1 and PLC-{beta}3 via G{alpha}q and G{beta}{gamma}i, respectively, resulting in inositol 1,4,5-trisphosphate-dependent Ca2+ release and MLCK-mediated MLC20 phosphorylation, and 2) sustained contraction exclusively mediated by S1P2 involving activation of RhoA via G{alpha}q and G{alpha}13, resulting in Rho kinase- and PKC-dependent MLC20 phosphorylation.

muscle contraction; signal transduction


Address for reprint requests and other correspondence: K. S. Murthy, Depts. of Physiology and Medicine, Medical College of Virginia Campus, Virginia Commonwealth Univ., Richmond, VA 23298.




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
J. Igarashi and T. Michel
Sphingosine-1-phosphate and modulation of vascular tone
Cardiovasc Res, May 1, 2009; 82(2): 212 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Skoura and T. Hla
Regulation of vascular physiology and pathology by the S1P2 receptor subtype
Cardiovasc Res, May 1, 2009; 82(2): 221 - 228.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. Ohama, M. Okada, T. Murata, D. L. Brautigan, M. Hori, and H. Ozaki
Sphingosine-1-phosphate enhances IL-1{beta}-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts
Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G766 - G775.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. S. Murthy
Inhibitory Phosphorylation of Soluble Guanylyl Cyclase by Muscarinic m2 Receptors via G{beta}{gamma}-Dependent Activation of c-Src Kinase
J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 183 - 189.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Rattan and C. A. Patel
Selectivity of ROCK inhibitors in the spontaneously tonic smooth muscle
Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G687 - G693.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. S. Murthy and W. Sriwai
Stimulatory phosphorylation of cAMP-specific PDE4D5 by contractile agonists is mediated by PKC-dependent inactivation of protein phosphatase 2A
Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G327 - G335.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
B. You, A. Ren, G. Yan, and J. Sun
Activation of Sphingosine Kinase-1 Mediates Inhibition of Vascular Smooth Muscle Cell Apoptosis by Hyperglycemia
Diabetes, May 1, 2007; 56(5): 1445 - 1453.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. A. Patel and S. Rattan
Spontaneously tonic smooth muscle has characteristically higher levels of RhoA/ROK compared with the phasic smooth muscle
Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G830 - G837.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. Hu, S. Mahavadi, J. Huang, F. Li, and K. S. Murthy
Characterization of S1P1 and S1P2 receptor function in smooth muscle by receptor silencing and receptor protection
Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G605 - G610.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
T. Hashimoto, M. Kihara, J. Ishida, N. Imai, S.-i. Yoshida, Y. Toya, A. Fukamizu, H. Kitamura, and S. Umemura
Apelin Stimulates Myosin Light Chain Phosphorylation in Vascular Smooth Muscle Cells
Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1267 - 1272.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. S. Jolly, M. Bektas, K. R. Watterson, H. Sankala, S. G. Payne, S. Milstien, and S. Spiegel
Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors
Blood, June 15, 2005; 105(12): 4736 - 4742.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. Huang, H. Zhou, S. Mahavadi, W. Sriwai, V. Lyall, and K. S. Murthy
Signaling pathways mediating gastrointestinal smooth muscle contraction and MLC20 phosphorylation by motilin receptors
Am J Physiol Gastrointest Liver Physiol, January 1, 2005; 288(1): G23 - G31.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
V. McNeil Coffield, W. S. Helms, Q. Jiang, and L. Su
G{alpha}13 Mediates a Signal That Is Essential for Proliferation and Survival of Thymocyte Progenitors
J. Exp. Med., November 15, 2004; 200(10): 1315 - 1324.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
E. Hersch, J. Huang, J. R. Grider, and K. S. Murthy
Gq/G13 signaling by ET-1 in smooth muscle: MYPT1 phosphorylation via ETA and CPI-17 dephosphorylation via ETB
Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1209 - C1218.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.