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K + secretion activated by luminal P2Y 2 and P2Y 4 receptors in mouse colon
Author(s) -
Matos J. E.,
Robaye B.,
Boeynaems J. M.,
Beauwens R.,
Leipziger J.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.080002
Subject(s) - p2y receptor , receptor , secretion , ussing chamber , medicine , endocrinology , extracellular , chemistry , ion transporter , intestinal mucosa , patch clamp , biology , purinergic receptor , microbiology and biotechnology , biochemistry , membrane
Extracellular nucleotides are important regulators of epithelial ion transport, frequently exerting their action from the luminal side. Luminal P2Y receptors have previously been identified in rat distal colonic mucosa. Their activation by UTP and ATP stimulates K + secretion. The aim of this study was to clarify which of the P2Y receptor subtypes are responsible for the stimulated K + secretion. To this end P2Y 2 and P2Y 4 knock‐out mice were used to measure distal colonic ion transport in an Ussing chamber. In mouse (NMRI) distal colonic mucosa, luminal UTP and ATP with similar potency induced a rapid and transient increase of the transepithelial voltage ( V te ) (UTP: from −0.81 ± 0.23 to 3.11 ± 0.61 mV, n = 24), an increase of equivalent short circuit current ( I sc ) by 166.9 ± 22.8 μA cm −2 and a decrease of transepithelial resistance ( R te ) from 29.4 ± 2.4 to 23.5 ± 2.0 Ω cm 2 . This effect was completely inhibited by luminal Ba 2 + (5 m m , n = 5) and iberiotoxin (240 n m , n = 6), indicating UTP/ATP‐stimulated K + secretion. RT‐PCR analysis of isolated colonic crypts revealed P2Y 2 , P2Y 4 and P2Y 6 specific transcripts. The luminal UTP‐stimulated K + secretion was still present in P2Y 2 receptor knock‐out mice, but significantly reduced (Δ V te : 0.83 ± 0.26 mV) compared to wild‐type littermates (Δ V te : 2.08 ± 0.52 mV, n = 9). In P2Y 4 receptor knock‐out mice the UTP‐induced K + secretion was similarly reduced. Luminal UTP‐stimulated K + secretion was completely absent in P2Y 2 /P2Y 4 double receptor KO mice. Basolateral UTP showed no effect. In summary, these results indicate that both the P2Y 2 and P2Y 4 receptors are present in the luminal membrane of mouse distal colonic mucosa, and stimulation of these receptors leads to K + secretion.