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Basolateral PAR‐2 receptors mediate KCl secretion and inhibition of Na + absorption in the mouse distal colon
Author(s) -
Cuffe John E.,
Bertog Marko,
VelázquezRocha Sara,
Dery Olivier,
Bunnett Nigel,
Korbmacher Christoph
Publication year - 2002
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.2001.013159
Subject(s) - amiloride , bumetanide , chemistry , receptor , endocrinology , extracellular , ion transporter , medicine , stimulation , secretion , microbiology and biotechnology , biophysics , biology , sodium , biochemistry , organic chemistry , membrane
Proteinase‐activated receptor‐2 (PAR‐2) may participate in epithelial ion transport regulation. Here we examined the effect of mouse activating peptide (mAP), a specific activator of PAR‐2, on electrogenic transport of mouse distal colon using short‐circuit current ( I SC ) measurements. Under steady‐state conditions, apical application of amiloride (100 μ m ) revealed a positive I SC component of 74.3 ± 6.8 μA cm −2 indicating the presence of Na + absorption, while apical Ba 2+ (10 m m ) identified a negative I SC component of 26.2 ± 1.8 μA cm −2 consistent with K + secretion. Baseline Cl − secretion was minimal. Basolateral addition of 20 μ m mAP produced a biphasic I SC response with an initial transient peak increase of 11.2 ± 0.9 μA cm −2 , followed by a sustained fall to a level 31.2 ± 2.6 μA cm −2 ( n = 43 ) below resting I SC . The peak response was due to Cl − secretion as it was preserved in the presence of amiloride but was largely reduced in the presence of basolateral bumetanide (20 μ m ) or in the absence of extracellular Cl − . The secondary decline of I SC was also attenuated by bumetanide and by Ba 2+ , indicating that it is partly due to a stimulation of K + secretion. In addition, the amiloride‐sensitive I SC was slightly reduced by mAP, suggesting that inhibition of Na + absorption also contributes to the I SC decline. Expression of PAR‐2 in mouse distal colon was confirmed using RT‐PCR and immunocytochemistry. We conclude that functional basolateral PAR‐2 is present in mouse distal colon and that its activation stimulates Cl − and K + secretion while inhibiting baseline Na + absorption.