For Manuscript Submission, Check or Review Login please go to Submission Websites List.
For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.
Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal TubuleQueiroz-Leite G.D.a · Crajoinas R.O.b · Neri E.A.a · Bezerra C.N.A.a · Girardi A.C.C.b · Rebouças N.A.a · Malnic G.a
aDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, bHeart Institute (InCor), Medical School, University of São Paulo São Paulo, Brazil Corresponding Author
Gabriella Duarte Queiroz-Leite
Department of Physiology and Biophysics, Institute of Biomedical Sciences
University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, 05508-900 SP (Brazil)
Tel. +55-11-3091-7280, Fax +55-11-3091-9922, E-Mail email@example.com
Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na+ excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO3- reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH4Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na+ reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension.
© 2012 S. Karger AG, Basel