Purinergic receptors mediate cell proliferation and enhanced recovery from renal ischemia by adenosine triphosphate

Mark S. Paller, Eric J. Schnaith, Mark E. Rosenberg

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26 Scopus citations


Kidney dysfunction after ischemia can be improved by either limiting the initial injury or by enhancing the subsequent proliferative repair process. Adenasine triphosphate (ATP) favorably affects kidney function when it is given shortly after ischemia. We tested whether ATP promotes the proliferative repair response. Rats were subjected to occlusion of the left renal artery for 40 minutes and received an infusion of ATP, 12.5 μmol intravenously over 30 minutes, beginning at reperfusion. Control animals received saline solution or the hydroxyl radical scavenger dimethylthiourea (DMTU). Despite comparable functional protection by DMTU and ATP, only ATP specifically increased DNA synthesis (renal incorporation of tritiated thymidine) to an extent greater than that produced by ischemia alone. In other animals, ribonucleic acid was extracted from kidneys for Northern analysis. Expression of the proto-oncogenes c-fos and c-jun was enhanced in ATP-treated animals as compared with controls. Expression of a hone protein gene (H2b) and thymidine kinase was increased by ischemia but was not additionally affected by ATP. In vitro studies of primary cultures of renal proximal tubule epithelial cells confirmed the ability of ATP to stimulate cellular proliferation as a consequence of stimulation of purinergic P2 receptors, possibly of the P2x subclass. In summary, ATP given after ischemia increased new DNA synthesis and augmented expression of genes critical to cellular proliferation. These beneficial effects were not merely a consequence of limiting initial cellular damage, and they suggest a novel mechanism of action for ATP and other purinergic receptor agonists in renal ischemia.

Original languageEnglish (US)
Pages (from-to)174-183
Number of pages10
JournalJournal of Laboratory and Clinical Medicine
Issue number2
StatePublished - 1998

Bibliographical note

Funding Information:
From the Department of Medicine, University of Minnesota. Supported in part by an American Heart Association Grant-In-Aid (M.S.P.) and a Young Investigator Grant from the National Kidney Foundation (M.E.R.). At the time of these studies Dr. Schnaith was the recipient of a medical student grant from the Minnesota Medical Foundation. Presented in abstract form at Annual Meetings of the American Society of Nephrology, December 1990 and November 1996. Submitted for publication July 10, 1997; revision submitted Sept. 23, 1997; accepted Oct. 3, 1997. Reprint requests: Mm~kS . Paller, MD, Universityo f Minnesota, Box 736, UMHC, 420 Delaware Street SE, Minneapolis MN 55455. Copyright © 1998 by Mosby, Inc. 0022-2143/98 $5.00 + 0 5/1/86793


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