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

Open Access
Publisher Website
Google Scholar
Abstract
To clarify the role of the PGI2/PGI2receptor (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 PGI2signals, we compared the effects of different PGI2analogs [iloprost (ILP), carba-prostacyclin (c-PGI2), and cicaprost (CCP)] in the isolated perfused RCCD. PGI2analogs did not increase water flow ( Lp). Although PGI2analogs did not reduce an established Lpresponse to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated Lpby 45%. The inhibitory effect of ILP and c-PGI2on AVP-stimulated Lpis 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 PGE2increased [Ca2+]i, suggesting that CCP did not cause desensitization to either ILP or PGE2. We concluded that ILP and c-PGI2activate PKC and the liberation of [Ca2+]ibut not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI2effects but not CCP in RCCD.