Effect of uroguanylin on potassium and bicarbonate transport in rat renal tubules

Abstract

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 ± 10−6mol 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). JKincreased from 0.63 ± 0.06 nmol·cm–2·s–1in 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 10−7mol iberiotoxin/L, the UGN effect was abolished: JKwas 0.37 ± 0.038 nmol·cm–2·s–1in 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 10−4mol 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.