title: Distal colonic Na(+) absorption inhibited by luminal P2Y(2) receptors.
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 P2Y(2) and a luminal P2Y(4) 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 Omega cm(2), equivalent short circuit current (I (sc)): -563.9 +/- 63.8 microA/cm(2) (n = 21). Amiloride completely inhibited I (sc) to -0.5 +/- 8.5 microA/cm(2). Luminal ATP induced a slowly on-setting and persistent inhibition of the amiloride-sensitive I (sc) by 160.7 +/- 29.7 microA/cm(2) (n = 12, NMRI mice). Luminal ATP and UTP were almost equipotent with IC(50) values of 10 microM and 3 microM respectively. In P2Y(2) knock-out (KO) mice, the effect of luminal UTP on amiloride-sensitve Na(+) absorption was absent. In contrast, in P2Y(4) 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 P2Y(2) and P2Y(4) receptors and ENaC channels co-localize in surface epithelium. Intriguingly, only the stimulation of the P2Y(2) receptor mediates inhibition of electrogenic Na(+) absorption.
authors.affiliation: Institute of Physiology and Biophysics, The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark.
authors.forename: J E
authors.initials: JE
authors.lastname: Matos
authors.forename: M V
authors.initials: MV
authors.lastname: Sorensen
authors.forename: C S
authors.initials: CS
authors.lastname: Geyti
authors.forename: B
authors.initials: B
authors.lastname: Robaye
authors.forename: J M
authors.initials: JM
authors.lastname: Boeynaems
authors.forename: J
authors.initials: J
authors.lastname: Leipziger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004039:Diet, Sodium-Restricted; D015194:Diffusion Chambers, Culture; D004232:Diuretics / Q000494:pharmacology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009711:Nucleotides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D058473:Receptors, Purinergic P2Y2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D013045:Species Specificity; D014544:Uridine Triphosphate / Q000378:metabolism
chemical_list: D004232:Diuretics; D009711:Nucleotides; C546386:P2ry2 protein, mouse; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D007041:Hypoxanthine Phosphoribosyltransferase; D014544:Uridine Triphosphate