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Hypotonicity-Induced Renin Exocytosis from Juxtaglomerular Cells Requires Aquaporin-1 and Cyclooxygenase-2

Ulla G. Friis^*, Kirsten Madsen^*, Per Svenningsen^*, Pernille B.L. Hansen^*, Ambika Gulaveerasingam^*, Finn Jørgensen^*, Christian Aalkjær, Ole Skøtt^* and Boye L. Jensen^*

*Department of Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, Odense, Denmark; and
Department of Physiology, University of Aarhus, Aarhus, Denmark

Correspondence: Dr. Ulla G. Friis, Department of Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, J. B. Winsloewsvej 21, 3., DK-5000 Odense, Denmark. Phone: +45-65503754; Fax: +45-66133479; E-mail: ufriis{at}health.sdu.dk

Received for publication September 8, 2008. Accepted for publication May 25, 2009.

The mechanism by which extracellular hypotonicity stimulates release of renin from juxtaglomerular (JG) cells is unknown. We hypothesized that osmotically induced renin release depends on water movement through aquaporin-1 (AQP1) water channels and subsequent prostanoid formation. We recorded membrane capacitance (C_m) by whole-cell patch clamp in single JG cells as an index of exocytosis. Hypotonicity increased C_m significantly and enhanced outward current. Indomethacin, PLA₂ inhibition, and an antagonist of prostaglandin transport impaired the C_m and current responses to hypotonicity. Hypotonicity also increased exocytosis as determined by a decrease in single JG cell quinacrine fluorescence in an indomethacin-sensitive manner. In single JG cells from COX-2^{–/ –} and AQP1^{–/ –} mice, hypotonicity increased neither C_m nor outward current, but 0.1-µM PGE₂ increased both in these cells. A reduction in osmolality enhanced cAMP accumulation in JG cells but not in renin-producing As4.1 cells; only the former had detectable AQP1 expression. Inhibition of protein kinase A blocked the hypotonicity-induced C_m and current response in JG cells. Taken together, our results show that a 5 to 7% decrease in extracellular tonicity leads to AQP1-mediated water influx in JG cells, PLA₂/COX-2-mediated prostaglandin-dependent formation of cAMP, and activation of PKA, which promotes exocytosis of renin.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673