title: Characterization of flow-regulated cortical collecting duct endothelin-1 production.
abstract: Collecting duct (CD) endothelin-1 (ET-1) is an autocrine inhibitor of Na+and water reabsorption. Salt or water loading increases CD ET-1 production; this is likely due, at least in part, to increased tubule fluid flow. The mechanisms by which flow stimulates CD ET-1 production are incompletely understood. In particular, flow induction of cortical CD (CCD) and inner medullary CD (IMCD) ET-1 synthesis may occur via different mechanisms. Since flow-mediated ET-1 production in IMCD has been more extensively characterized than in the CCD, this study was undertaken to further examine putative signaling pathways involved in flow-stimulated CCD ET-1 production. The CD cell line, mpkCCDcl4, was exposed to static or flow (2 dyne/cm2for 2 h) conditions and ET-1/GAPDH mRNA levels were assessed. Intracellular Ca2+, Ca2+-stimulated Ca2+release, calcineurin, and protein kinase cα/βisoforms were all involved in the ET-1 flow response. TRPC6, but not other CD-expressed TRP channels (TRPC3, 4, and 5, or TRPV4) played a role in the ET-1 flow response. Purinergic signaling pathways and cilia were not involved in the ET-1 flow response. Based on these and previously published findings, we present a comparison of flow-stimulated CD ET-1 production between CCD and IMCD We suggest that flow-stimulated CCD ET-1 production may be more involved in responding to Na+delivery, while IMCD ET-1 production may be more responsive to water and solute delivery; the responsible pathways for mediating these effects in the two regions of the CD appear to be substantially distinct from one another.
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Ramkumar
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah donald.kohan@hsc.utah.edu.|Salt Lake VA Medical Center, Salt Lake City, Utah.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D019332:Endothelin-1 / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019332:Endothelin-1; D011493:Protein Kinase C; D019703:Calcineurin; D002118:Calcium
keywords: Collecting duct; cortical; endothelin; flow; medullary; signaling