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Luminal and basolateral endothelin inhibit chloride reabsorption in the mouse thick ascending limb via a Ca 2+ ‐Independent Pathway
Author(s) -
Ferreira Marie Celeste,
Bailly Claire
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.749ba.x
Subject(s) - protein kinase c , chemistry , staurosporine , endothelin receptor , receptor , reabsorption , endothelin 1 , endocrinology , medicine , biophysics , biochemistry , signal transduction , biology , kidney
1 The recent localization of endothelin synthesis and receptors in the thick ascending limb (TAL) prompted us to investigate a possible autocrine and/or paracrine effect of this agent. The net chloride flux ( J Cl ) has been determined in isolated cortical and medullary TALs by the in vitro microperfusion technique. 2 In both segments, endothelin 1 (ET‐1) at 10 −8 m in the bath significantly decreased J Cl , an effect which was partially reversible and observed at concentrations equal to or greater than 10 −13 m . 3 This ( J Cl inhibition (by 33.9 ± 3.2%) was blocked by BQ788 and was also observed with sarafotoxin 6 C and ET‐3, indicating that endothelin receptor B (ET B ) are present in TAL. 4 ET‐1 did not affect cAMP content under basal or hormone‐stimulated conditions. The presence of a prostaglandin synthesis inhibitor also did not prevent the ET‐1 action on J Cl . 5 The ET‐1‐induced inhibition of J Cl was prevented by protein kinase C inhibitors (staurosporine or GF 109203) and was reproduced by diacylglycerol analogues (OAG and D i C 8 ). However, ET‐1 failed to increase intracellular Ca 2+ concentration. 6 Addition of ET‐1 or ET‐3 to the apical surface induced a decrease of J Cl through ET B receptors, an effect which was not additive with that induced by basolateral ET‐1, and was not concomitant with an increase in intracellular Ca 2+ concentration. 7 It is concluded that the basolateral and luminal inhibitions of J Cl by ET‐1 in TAL, through ET B receptors, is mediated by a protein kinase C activation which is independent of intracellular Ca 2+ increase.