Distal colonic Na+ absorption inhibited by luminal P2Y2 receptors |
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Authors: | J E Matos M V Sorensen C S Geyti B Robaye J M Boeynaems J Leipziger |
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Institution: | (1) Institute of Physiology and Biophysics, The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark;(2) Institute of Interdisciplinary Research, Institute of Biology and Molecular Medicine, Université Libre de Bruxelles, Gosselies, Belgium;(3) Laboratory of Medical Chemistry, Erasme Hospital, Université Libre de Bruxelles, Gosselies, Belgium;(4) Ole Worms Allé 160, 8000 Aarhus, Denmark |
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Abstract: | Luminal P2 receptors are ubiquitously expressed in transporting epithelia. In steroid-sensitive epithelia (e.g., lung, distal
nephron) epithelial Na+ channel (ENaC)-mediated Na+ absorption is inhibited via luminal P2 receptors. In distal mouse colon, we have identified that both, a luminal P2Y2 and a luminal P2Y4 receptor, stimulate K+ secretion. In this study, we investigate the effect of luminal adenosine triphosphate/uridine triphosphate (ATP/UTP) on electrogenic
Na+ absorption in distal colonic mucosa of mice treated on a low Na+ diet for more than 2 weeks. Transepithelial electrical parameters were recorded in an Ussing chamber. Baseline parameters:
transepithelial voltage (V
te): −13.7 ± 1.9 mV (lumen negative), transepithelial resistance (R
te): 24.1 ± 1.8 Ω cm2, equivalent short circuit current (I
sc): −563.9 ± 63.8 μA/cm2 (n = 21). Amiloride completely inhibited I
sc to −0.5 ± 8.5 μA/cm2. Luminal ATP induced a slowly on-setting and persistent inhibition of the amiloride-sensitive I
sc by 160.7 ± 29.7 μA/cm2 (n = 12, NMRI mice). Luminal ATP and UTP were almost equipotent with IC50 values of 10 μM and 3 μM respectively. In P2Y2 knock-out (KO) mice, the effect of luminal UTP on amiloride-sensitve Na+ absorption was absent. In contrast, in P2Y4 KO mice the inhibitory effect of luminal UTP on Na+ absorption remained present. Semiquantitative polymerase chain reaction did not indicate regulation of the P2Y receptors
under low Na+ diet, but it revealed a pronounced axial expression of both receptors with highest abundance in surface epithelia. Thus,
luminal P2Y2 and P2Y4 receptors and ENaC channels co-localize in surface epithelium. Intriguingly, only the stimulation of the P2Y2 receptor mediates inhibition of electrogenic Na+ absorption. |
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Keywords: | P2Y2 knock-out P2Y4 knock-out Na+ transport Luminal P2 receptor UTP |
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