AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 296: H33-H42, 2009. First published November 14, 2008; doi:10.1152/ajpheart.00097.2008
0363-6135/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
296/1/H33    most recent
00097.2008v1
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 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 Google Scholar
Google Scholar
Right arrow Articles by Lee, J.-F.
Right arrow Articles by Lee, M.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J.-F.
Right arrow Articles by Lee, M.-J.

TRANSLATIONAL PHYSIOLOGY

Balance of S1P1 and S1P2 signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature

Jen-Fu Lee,1 Sharon Gordon,2 Rosendo Estrada,1 Lichun Wang,1 Deanna L. Siow,3 Binks W. Wattenberg,3,4,5 David Lominadze,2,* and Menq-Jer Lee1,6,*

1Gheens Center on Aging and Departments of 2Physiology and Biophysics, 3Biochemistry and Molecular Biology, 4Medicine, 5Pharmacology and Toxicology, and 6Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, Kentucky

Submitted 30 January 2008 ; accepted in final form 3 November 2008

Sphingosine-1-phosphate (S1P) regulates various molecular and cellular events in cultured endothelial cells, such as cytoskeletal restructuring, cell-extracellular matrix interactions, and intercellular junction interactions. We utilized the venular leakage model of the cremaster muscle vascular bed in Sprague-Dawley rats to investigate the role of S1P signaling in regulation of microvascular permeability. S1P signaling is mediated by the S1P family of G protein-coupled receptors (S1P1-5 receptors). S1P1 and S1P2 receptors, which transduce stimulatory and inhibitory signaling, respectively, are expressed in the endothelium of the cremaster muscle vasculature. S1P administration alone via the carotid artery was unable to protect against histamine-induced venular leakage of the cremaster muscle vascular bed in Sprague-Dawley rats. However, activation of S1P1-mediated signaling by SEW2871 and FTY720, two agonists of S1P1, significantly inhibited histamine-induced microvascular leakage. Treatment with VPC 23019 to antagonize S1P1-regulated signaling greatly potentiated histamine-induced venular leakage. After inhibition of S1P2 signaling by JTE-013, a specific antagonist of S1P2, S1P was able to protect microvascular permeability in vivo. Moreover, endothelial tight junctions and barrier function were regulated by S1P1- and S1P2-mediated signaling in a concerted manner in cultured endothelial cells. These data suggest that the balance between S1P1 and S1P2 signaling regulates the homeostasis of microvascular permeability in the peripheral circulation and, thus, may affect total peripheral vascular resistance.

spingosine-1-phosphate receptor subtypes; vascular integrity; signal transduction


Addresses for reprint requests and other correspondence: D. Lominadze, Dept. of Physiology and Biophysics, School of Medicine, Univ. of Louisville, 580 S. Preston St., Louisville, KY 40202 (e-mail: dglomi01{at}louisville.edu); M. J. Lee, Dept. of Microbiology and Immunology, School of Medicine, Univ. of Louisville, 580 S. Preston St., Louisville, KY 40202 (e-mail: menqjer.lee{at}louisville.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.