biostudies-literatureHu LNational Natural Science Foundation of China111202https://www.ebi.ac.uk/biostudies/studies/S-EPMC12925561biostudies-literatureUnknown302(3)Endothelin-1 (ET-1) from renal-tubule-epithelial-cells inhibits NaCl reabsorption via ET_B receptor in an autocrine manner, and inhibition of ET_B receptors leads to salt-sensitive-hypertension. In the distal convoluted tubule (DCT), NaCl enters the cell via NaCl-cotransporter (NCC) and Cl^- exits the cell in part by ClC-K2 channels, which play a role in regulating With-No-lysine kinase 4 (WNK4). The study aims to explore whether ET-1-induced inhibition of NaCl absorption is also achieved by inhibiting the basolateral Cl^- channels in the DCT. Patch-clamp and immunoblotting assessed ET-1 effects on DCT Cl^- channels and NCC. Immunofluorescence images detected ETB-receptor expression in parvalbumin-positive DCT. Application of ET-1 decreasedThe Journal of biological chemistryNitric oxide mediates ET-1-induced-inhibition of NPPB-sensitive Cl<sup>-</sup> currents in the early distal convoluted tubule of the mouse kidney.PMC129255618190065232360215Wang MYou YQiu HZhang HHu LMeng XXiao AfalseNitric oxide mediates ET-1-induced-inhibition of NPPB-sensitive Cl<sup>-</sup> currents in the early distal convoluted tubule of the mouse kidney.Endothelin-1 (ET-1) from renal-tubule-epithelial-cells inhibits NaCl reabsorption via ET_B receptor in an autocrine manner, and inhibition of ET_B receptors leads to salt-sensitive-hypertension. In the distal convoluted tubule (DCT), NaCl enters the cell via NaCl-cotransporter (NCC) and Cl^- exits the cell in part by ClC-K2 channels, which play a role in regulating With-No-lysine kinase 4 (WNK4). The study aims to explore whether ET-1-induced inhibition of NaCl absorption is also achieved by inhibiting the basolateral Cl^- channels in the DCT. Patch-clamp and immunoblotting assessed ET-1 effects on DCT Cl^- channels and NCC. Immunofluorescence images detected ETB-receptor expression in parvalbumin-positive DCT. Application of ET-1 decreased2026-01-01T00:00:00Z2026 Jan2026-07-16T15:15:16.996Z2026-07-10T03:10:07.801ZS-EPMC129255614158187810.1016/j.jbc.2026.111202