title: Fructose acutely stimulates NHE3 activity in kidney proximal tubule.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo São Paulo, Brazil. gabidq@icb.usp.br
authors.forename: Gabriella D
authors.initials: GD
authors.lastname: Queiroz-Leite
authors.forename: Renato O
authors.initials: RO
authors.lastname: Crajoinas
authors.forename: Elida A
authors.initials: EA
authors.lastname: Neri
authors.forename: Camila N A
authors.initials: CN
authors.lastname: Bezerra
authors.forename: Adriana C C
authors.initials: AC
authors.lastname: Girardi
authors.forename: Nancy Amaral
authors.initials: NA
authors.lastname: Rebouças
authors.forename: Gerhard
authors.initials: G
authors.lastname: Malnic
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005631:Fructokinases / Q000378:metabolism; D005632:Fructose / Q000494:pharmacology*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018374:LLC-PK1 Cells; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013552:Swine
chemical_list: D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; C495683:Slc2a2 protein, rat; C495727:Slc2a5 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D005632:Fructose; D000242:Cyclic AMP; D005631:Fructokinases; C021475:ketohexokinase; D017868:Cyclic AMP-Dependent Protein Kinases