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- Title
Distal colonic Na<sup>+</sup> absorption inhibited by luminal P2Y<sub>2</sub> receptors.
- Authors
Matos, J. E.; Sorensen, M. V.; Geyti, C. S.; Robaye, B.; Boeynaems, J. M.; Leipziger, J.
- 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.
- Subjects
EPITHELIUM; STEROIDS; KIDNEY tubules; ADENOSINE triphosphate; BIOLOGICAL transport
- Publication
Pflügers Archiv: European Journal of Physiology, 2007, Vol 454, Issue 6, p977
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-007-0248-9