Localization of IP in rabbit kidney and functional role of the PGI(2)/IP system in cortical collecting duct.
To clarify the role of the PGI(2)/PGI(2) 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 PGI(2) signals, we compared the effects of different PGI(2) analogs [iloprost (ILP), carba-prostacyclin (c-PGI(2)), and cicaprost (CCP)] in the isolated perfused RCCD. PGI(2) analogs did not increase water flow (L(p)). Although PGI(2) analogs did not reduce an established L(p) response to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated L(p) by 45%. The inhibitory effect of ILP and c-PGI(2) on AVP-stimulated L(p) 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 Ca(2+) concentration ([Ca(2+)](i)), but, in the presence of CCP, individual infusion of ILP and PGE(2) increased [Ca(2+)](i), suggesting that CCP did not cause desensitization to either ILP or PGE(2). We concluded that ILP and c-PGI(2) activate PKC and the liberation of [Ca(2+)](i) but not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI(2) effects but not CCP in RCCD.
Nasrallah
Rania
R
Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ontario, Canada K1H 8M5.
Nusing
Rolf M
RM
Hébert
Richard L
RL
D000465:Algorithms; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D000242:Cyclic AMP / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism*; D007672:Kidney Cortex / Q000033:anatomy & histology / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism* / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects
D007202:Indicators and Reagents; D012333:RNA, Messenger; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D001127:Arginine Vasopressin; D011464:Epoprostenol; D000242:Cyclic AMP