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The vasopressin type 2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMP-independent pathway

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Aquaporin-2 membrane targeting: still a conundrum

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Aquaporin-2 membrane targeting: still a conundrum

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer

Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be cAMP dependent. However, on the basis of recent reports, it was hypothesized in the current study that increased cAMP levels are not necessary for AQP2 membrane targeting. The role and dynamics of cAMP signaling in AQP2 membrane targeting in Madin-Darby canine kidney and mouse cortical collecting duct (mpkCCD14) cells was examined using selective agonists against the V2R (dDAVP), EP2 (butaprost), and EP4 (CAY10580). During EP2 stimulation, AQP2 membrane targeting continually increased during 80 min of stimulation; whereas cAMP levels reached a plateau after 10 min. EP4 stimulation caused a rapid and transient increase in AQP2 membrane targeting, but did not significantly increase cAMP levels. After washout of the EP2 agonist or dDAVP, AQP2 membrane abundance remained elevated for at least 80 min, whereas cAMP levels rapidly decreased. Similar effects of the EP2 agonist were also observed for AQP2 constitutively nonphosphorylated at ser-269. The adenylyl cyclase inhibitor SQ22536 did not prevent AQP2 targeting during stimulation of each receptor, nor after dDAVP washout. In conclusion, this study demonstrates that although direct stimulation with cAMP causes AQP2 membrane targeting, cAMP is not necessary for receptor-mediated AQP2 membrane targeting and Gs-coupled receptors can also signal through an alternative pathway that increases AQP2 membrane targeting.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology - Renal Physiology
Vol/bind311
Udgave nummer5
Sider (fra-til)F935-F944
ISSN1931-857X
DOI
StatusUdgivet - 1 nov. 2016

ID: 49295448