Effect of uroguanylin on potassium and bicarbonate transport in rat renal tubules.
The effect of uroguanylin (UGN) on K+ and H+ secretion in the renal tubules of the rat kidney was studied using in vivo stationary microperfusion. For the study of K+ secretion, a tubule was punctured to inject a column of FDC-green-colored Ringer's solution with 0.5 mmol KCl/L+/-10(-6) mol UGN/L, and oil was used to block fluid flow. K+ activity and transepithelial potential differences (PD) were measured with double microelectrodes (K+ ion-selective resin vs. reference) in the distal tubules of the same nephron. During perfusion, K+ activity rose exponentially, from 0.5 mmol/L to stationary concentration, allowing for the calculation of K+ secretion (JK). JK increased from 0.63+/-0.06 nmol.cm-2.s-1 in the control group to 0.85+/-0.06 in the UGN group (p<0.01). PD was -51.0+/-5.3 mV in the control group and -50.3+/-4.98 mV in the UGN group. In the presence of 10(-7) mol iberiotoxin/L, the UGN effect was abolished: JK was 0.37+/-0.038 nmol.cm-2.s-1 in the absence of, and 0.38+/-0.025 in the presence of, UGN, indicating its action on maxi-K channels. In another series of experiments, renal tubule acidification was studied, using a similar method: proximal and distal tubules were perfused with solutions containing 25 mmol NaHCO3/L. Acidification half-time was increased both in proximal and distal segments and, as a consequence, bicarbonate reabsorption decreased in the presence of UGN (in proximal tubules, from 2.40+/-0.26 to 1.56+/-0.21 nmol.cm-2.s-1). When the Na+/H+ exchanger was inhibited by 10(-4) mol hexamethylene amiloride (HMA)/L, the control and UGN groups were not significantly different. In the late distal tubule, after HMA, UGN significantly reduced JHCO3-, indicating an effect of UGN on H+-ATPase. These data show that UGN stimulated JK+ by acting on maxi-K channels, and decreased JHCO3- by acting on NHE3 in proximal and H+-ATPase in distal tubules.
Amorim
José Benedito Oliveira
JB
Faculdade de Odontologia, S. José dos Campos, Unesp, Brazil.
Musa-Aziz
Raif
R
Lessa
Lucilia M A
LM
Malnic
Gerhard
G
Fonteles
Manassés Claudino
MC
D000465:Algorithms; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006207:Half-Life; D006859:Hydrogen / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008839:Microelectrodes; D045265:Natriuretic Peptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D001639:Bicarbonates; D045265:Natriuretic Peptides; D010455:Peptides; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C084362:uroguanylin; C064719:iberiotoxin; D006859:Hydrogen; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium