Release of ATP by TRPV4 activation is dependent upon the expression of AQP2 in renal cells

J Cell Physiol. 2021 Apr;236(4):2559-2571. doi: 10.1002/jcp.30013. Epub 2020 Aug 17.

Abstract

Increasing evidence indicates that aquaporins (AQPs) exert an influence in cell signaling by the interplay with the transient receptor potential vanilloid 4 (TRPV4) channel. We previously found that TRPV4 physically and functionally interacts with AQP2 in cortical collecting ducts (CCD) cells, favoring cell volume regulation and cell migration. Because TRPV4 was implicated in ATP release in several tissues, we investigated the possibility that TRPV4/AQP2 interaction influences ATP release in CCD cells. Using two CCD cell lines expressing or not AQP2, we measured extracellular ATP (ATPe) under TRPV4 activation and intracellular Ca2+ under ATP addition. We found that AQP2 is critical for the release of ATP induced by TRPV4 activation. This ATP release occurs by an exocytic and a conductive route. ATPe, in turn, stimulates purinergic receptors leading to ATPe-induced ATP release by a Ca2+ -dependent mechanism. We propose that AQP2 by modulating Ca2+ and ATP differently could explain AQP2-increased cell migration.

Keywords: ATP; TRPV4; aquaporin-2; cell migration; pannexin-1; purinergic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Aquaporin 2 / metabolism*
  • Autocrine Communication
  • Calcium / metabolism*
  • Calcium Signaling* / drug effects
  • Cell Line
  • Cell Movement* / drug effects
  • Exocytosis
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / metabolism*
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Paracrine Communication
  • Rats
  • Receptors, Purinergic P2 / metabolism
  • Sulfonamides / pharmacology
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / metabolism*

Substances

  • Aqp2 protein, rat
  • Aquaporin 2
  • N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide
  • Receptors, Purinergic P2
  • Sulfonamides
  • TRPV Cation Channels
  • Trpv4 protein, rat
  • Adenosine Triphosphate
  • Leucine
  • Calcium