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Activation of the metabolic sensor AMP-activated protein kinase inhibits aquaporin-2 function in kidney principal cells.

Authors :
Al-Bataineh, Mohammad M.
Hui Li
Kazuhiro Ohmi
Fan Gong
Marciszyn, Allison L.
Naveed, Sajid
Xiaoqing Zhu
Neumann, Dietbert
Qi Wu
Lei Cheng
Fenton, Robert A.
Pastor-Soler, Núria M.
Hallows, Kenneth R.
Source :
American Journal of Physiology: Renal Physiology. Nov2016, Vol. 311 Issue 5, pF890-F900. 11p.
Publication Year :
2016

Abstract

Aquaporin-2 (AQP2) is essential to maintain body water homeostasis. AQP2 traffics from intracellular vesicles to the apical membrane of kidney collecting duct principal cells in response to vasopressin [arginine vasopressin (AVP)], a hormone released with low intravascular volume, which causes decreased kidney perfusion. Decreased kidney perfusion activates AMP-activated kinase (AMPK), a metabolic sensor that inhibits the activity of several transport proteins. We hypothesized that AMPK activation also inhibits AQP2 function. These putative AMPK effects could protect interstitial ionic gradients required for urinary concentration during metabolic stress when low intravascular volume induces AVP release. Here we found that shortterm AMPK activation by treatment with 5-aminoimidazole-4-carboxamide- 1-α-D-ribofuranoside (AICAR; 75 min) in kidney tissue prevented baseline AQP2 apical accumulation in principal cells, but did not prevent AQP2 apical accumulation in response to the AVP analog desmopressin (dDAVP). Prolonged AMPK activation prevented AQP2 cell membrane accumulation in response to forskolin in mouse collecting duct mpkCCDc14 cells. Moreover, AMPK inhibition accelerated hypotonic lysis of Xenopus oocytes expressing AQP2. We performed phosphorylation assays to elucidate the mechanism by which AMPK regulates AQP2. Although AMPK weakly phosphorylated immunoprecipitated AQP2 in vitro, no direct AMPK phosphorylation of the AQP2 COOH-terminus was detected by mass spectrometry. AMPK promoted Ser-261 phosphorylation and antagonized dDAVP-dependent phosphorylation of other AQP2 COOH-terminal sites in cells. Our findings suggest an increasing, time-dependent antagonism of AMPK on AQP2 regulation with AICAR-dependent inhibition of cAMP-dependent apical accumulation and AVP-dependent phosphorylation of AQP2. This inhibition likely occurs via a mechanism that does not involve direct AQP2 phosphorylation by AMPK. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1931857X
Volume :
311
Issue :
5
Database :
Academic Search Index
Journal :
American Journal of Physiology: Renal Physiology
Publication Type :
Academic Journal
Accession number :
119563113
Full Text :
https://doi.org/10.1152/ajprenal.00308.2016