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Am J Physiol Renal Physiol 283: F689-F698, 2002. First published May 7, 2002; doi:10.1152/ajprenal.00020.2002
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Vol. 283, Issue 4, F689-F698, October 2002

Localization of IP in rabbit kidney and functional role of the PGI2/IP system in cortical collecting duct

Rania Nasrallah1, Rolf M. Nusing2, and Richard L. Hébert1

1 Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5; and 2 Department of Experimental Pediatrics and Clinical Pharmacology, Faculty of Medicine, Philipps University of Marburg, 35033 Marburg, Germany

To clarify the role of the PGI2/PGI2 receptor (IP) system in rabbit cortical collecting duct (RCCD), we characterized the expression of IP receptors in the rabbit kidney. We show by Northern and Western blotting that IP mRNA and protein was detectable in all three regions of the kidney. To determine how PGI2 signals, we compared the effects of different PGI2 analogs [iloprost (ILP), carba-prostacyclin (c-PGI2), and cicaprost (CCP)] in the isolated perfused RCCD. PGI2 analogs did not increase water flow (Lp). Although PGI2 analogs did not reduce an established Lp response to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated Lp by 45%. The inhibitory effect of ILP and c-PGI2 on AVP-stimulated Lp is partially reversed by the protein kinase C inhibitor staurosporine and abolished by pertussis toxin; no effect was obtained with CCP. In fura 2-loaded RCCD, CCP did not alter cytosolic Ca2+ concentration ([Ca2+]i), but, in the presence of CCP, individual infusion of ILP and PGE2 increased [Ca2+]i, suggesting that CCP did not cause desensitization to either ILP or PGE2. We concluded that ILP and c-PGI2 activate PKC and the liberation of [Ca2+]i but not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI2 effects but not CCP in RCCD.

cortical collecting duct; intracellular calcium; prostaglandin I2; transepithelial voltage; vasopressin; water transport


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