HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/F565    most recent 00023.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Okusa, M. D. Articles by Lynch, K. R. Search for Related Content PubMed PubMed Citation Articles by Okusa, M. D. Articles by Lynch, K. R.

Selective blockade of lysophosphatidic acid LPA₃ receptors reduces murine renal ischemia-reperfusion injury

Departments of ¹Medicine, ²Chemistry, and ³Pharmacology, University of Virginia, Charlottesville, Virginia 22908

Submitted 17 January 2003 ; accepted in final form 21 May 2003

Lysophosphatidic acid (LPA) released during ischemia has diverse physiological effects via its G protein-coupled receptors, LPA₁, LPA₂, and LPA₃ (formerly Edg-2, -4, and -7). We tested the hypothesis that selective blockade of LPA receptors affords protection from renal ischemia-reperfusion (I/R) injury. By real-time PCR, LPA_1-3 receptor mRNAs were expressed in mouse renal cortex, outer medulla, and inner medulla with the following rank order LPA₃ = LPA₂ > LPA₁. In C57BL/6 mice whose kidneys were subjected to ischemia and reperfusion, treatment with a selective LPA₃ agonist, oleoyl-methoxy phosphothionate (OMPT), enhanced injury. In contrast, a dual LPA₁/LPA₃-receptor antagonist, VPC-12249, reduced I/R injury, but this protective effect was lost when the antagonist was coadministered with OMPT. Interestingly, delaying administration of VPC-12249 until 30 min after the start of reperfusion did not alter its efficacy significantly. We conclude that VPC-12249 reduces renal I/R injury predominantly by LPA₃ receptor blockade and could serve as a novel compound in the treatment of ischemia acute renal failure.

VPC-12249; oleoyl-methoxy phosphothionate; kidney; acute renal failure

This article has been cited by other articles:

				J.-P. Pradere, J. Klein, S. Gres, C. Guigne, E. Neau, P. Valet, D. Calise, J. Chun, J.-L. Bascands, J.-S. Saulnier-Blache, et al. LPA1 Receptor Activation Promotes Renal Interstitial Fibrosis J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3110 - 3118. [Abstract] [Full Text] [PDF]

				A. S. Awad, H. Ye, L. Huang, L. Li, F. W. Foss Jr., T. L. Macdonald, K. R. Lynch, and M. D. Okusa Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1516 - F1524. [Abstract] [Full Text] [PDF]