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Originally published In Press as doi:10.1074/jbc.M505852200 on August 10, 2005

J. Biol. Chem., Vol. 280, Issue 41, 35028-35037, October 14, 2005
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Characterization of a Rabbit Kidney Prostaglandin F2{alpha} Receptor Exhibiting Gi-restricted Signaling That Inhibits Water Absorption in the Collecting Duct*

Richard L. Hébert{ddagger}, Monica Carmosino§, Osamu Saito§, Guangrui Yang¶, Cynthia A. Jackson§, Zhonghua Qi§, Richard M. Breyer§, Chandramohan Natarajan§, Aaron N. Hata§, Yahua Zhang§, Youfei Guan§, and Matthew D. Breyer§1

From the {ddagger}Departments of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada, the Department of Physiology, Peking University Health Science Center, Beijing, China 100083, and the §Division of Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee 37232

PGF2{alpha} is the most abundant prostaglandin detected in urine; however, its renal effects are poorly characterized. The present study cloned a PGF-prostanoid receptor (FP) from the rabbit kidney and determined the functional consequences of its activation. Nuclease protection assay showed that FP mRNA expression predominates in rabbit ovary and kidney. In situ hybridization revealed that renal FP expression predominates in the cortical collecting duct (CCD). Although FP receptor activation failed to increase intracellular Ca2+, it potently inhibited vasopressin-stimulated osmotic water permeability (Lp, 10-7 cm/(atm·s)) in in vitro microperfused rabbit CCDs. Inhibition of Lp by the FP selective agonist latanoprost was additive to inhibition of vasopressin action by the EP selective agonist sulprostone. Inhibition of Lp by latanoprost was completely blocked by pertussis toxin, consistent with a Gi-coupled mechanism. Heterologous transfection of the rabbit FPr into HEK293 cells also showed that latanoprost inhibited cAMP generation via a pertussis toxin-sensitive mechanism but did not increase cell Ca2+. These studies demonstrate a functional FP receptor on the basolateral membrane of rabbit CCDs. In contrast to the Ca2+ signal transduced by other FP receptors, this renal FP receptor signals via a PT-sensitive mechanism that is not coupled to cell Ca2+.


Received for publication, May 31, 2005 , and in revised form, July 21, 2005.

* This work was supported by National Institutes of Health Grant DK37097 (to M. D. B.). This work was also supported by the Kidney Foundation of Canada and by Canadian Institutes Health Research Grant MT-14103 (to R. L. H.), by Major National Basic Research Program of China Grants G2000056908, 30271521, and 303400810 (to Y. G.), and by National Institutes of Health Grant DK46205 (to R. M. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Div. of Nephrology and VAMC Vanderbilt University Nashville, TN 37232. Tel.: 615-327-4751 (ext. 5492); Fax: 615-343-4704; E-mail:: matthew.breyer{at}vanderbilt.edu.


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