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Acute and Chronic Effects of Prostaglandin E2 on NKCC2, NCC and ENaC in Ex Vivo Renal Tubules
Author(s) -
Esteva-Font Cristina,
Krogager Toke P.,
Hoorn Ewout J.,
Fenton Robert A.
Publication year - 2020
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.2020.34.s1.03263
Subject(s) - distal convoluted tubule , epithelial sodium channel , cotransporter , phosphorylation , chemistry , prostaglandin e2 , medicine , kidney , prostaglandin , endocrinology , ex vivo , reabsorption , microbiology and biotechnology , sodium , biochemistry , biology , in vitro , organic chemistry
The major renal prostaglandin, prostaglandin E2 (PGE2), is enzymatically generated from arachidonic acid in a series of steps catalyzed by various enzymes including Cox1/2. PGE2 has modulatory effects on renal Na+ handling, but the molecular targets of these effects in the distal segments of the renal tubule (TAL, DCT, CD) are less well characterized. Here, we assessed acute (30 minutes) and long‐term (24 h) actions of PGE2 (0.1 nM to 10 μM) on various Na+ transport proteins in these segments using tubule suspensions isolated from mouse kidney. In the long‐term, no significant effects could be detected on the abundance of the NaCl cotransporter NCC, the Na‐K‐Cl cotransporter NKCC2 or the epithelial Na+ channel ENaC (αENaC). Altered phosphorylation of NCC (T58) and NKCC2 (T105) or proteolytic cleavage of αENaC was not observed. Similar results were obtained in the presence of Cox1/2 inhibition and no sex differences were observed. Acutely, no effects on NKCC2 or αENaC were observed, but phosphorylation of NCC was decreased. A similar decrease in NCC phosphorylation was detected in NCC‐expressing MDCK cells. Data mining of online kidney RNAseq databases suggested that prostanoid receptor EP4 was expressed in the DCT, and ongoing studies are centered on determining if the actions of PGE2 on NCC are via this receptor. Support or Funding Information This project has received funding from The European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska‐Curie grant agreement no 754513, The Aarhus University Research Foundation and NNF Laureate Research Grant ‐ Novo Nordisk Fonden