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Flow regulation of endothelin‐1 production in the collecting duct
Author(s) -
Kohan Donald E,
LyonRoberts Brianna,
Strait Kevin A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1079.11
Subject(s) - chemistry , reabsorption , extracellular , epithelial sodium channel , intracellular , protein kinase c , endothelin 1 , endocrinology , medicine , amiloride , biophysics , sodium , biology , biochemistry , signal transduction , receptor , organic chemistry
Collecting duct (CD) endothelin‐1 (ET‐1) inhibits Na reabsorption. Salt loading increases CD ET‐1 production, however the responsible mechanisms are unknown. Tubule fluid flow increases in response to Na loading, hence we studied flow modulation of CD ET‐1. A high salt diet in mice increased inner medullary CD (IMCD) ET‐1 mRNA. Primary cultures of mouse IMCD detached in response to flow, consequently a CD cell line (mpkCCDcl4) was examined. Flow dose‐dependently increased ET‐1 mRNA between 2–10 dyne/cm2 and was first evident after 1 hr. Inhibition of calmodulin or dihydropyridine‐sensitive Ca channels did not alter the flow response, however chelation of intracellular Ca prevented flow‐stimulated ET‐1 mRNA accumulation. Flow increased intracellular Ca concentration as assessed by Fluo‐4 fluorescence. PKC inhibition markedly reduced flow‐stimulated ET‐1 mRNA levels. Flow‐stimulated ET‐1 synthesis was partially dependent upon sodium delivery since hypertonic NaCl perfusate increased, while absence of perfusate Na (replacing NaCl with choline Cl) decreased, flow‐stimulated ET‐1 mRNA. Amiloride partially reduced the ET‐1 response to flow. In summary, apical flow increases CD ET‐1 biosynthesis through intracellular Ca and PKC, and partly through apical Na channel Na transport. These studies suggest a novel pathway for coupling extracellular fluid volume to CD Na reabsorption.