Basolateral PAR-2 Receptors Mediate KCl Secretion and Inhibition of Na+ Absorption in the Mouse Distal Colon

J Physiol. 2002 Feb 15;539(Pt 1):209-22. doi: 10.1113/jphysiol.2001.013159.

Abstract

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 microM) revealed a positive I(SC) component of 74.3 +/- 6.8 microA x cm(-2) indicating the presence of Na+ absorption, while apical Ba2+ (10 mM) identified a negative I(SC) component of 26.2 +/- 1.8 microA x cm(-2) consistent with K+ secretion. Baseline Cl- secretion was minimal. Basolateral addition of 20 microM mAP produced a biphasic I(SC) response with an initial transient peak increase of 11.2 +/- 0.9 microA x cm(-2), followed by a sustained fall to a level 31.2 +/- 2.6 microA x 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 microM) or in the absence of extracellular Cl-. The secondary decline of I(SC) was also attenuated by bumetanide and by Ba2+, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorption / drug effects
  • Amiloride / pharmacology
  • Animals
  • Barium / pharmacology
  • Bumetanide / pharmacology
  • Chlorides / physiology
  • Colon / drug effects
  • Colon / metabolism*
  • Colon / physiology
  • Electric Conductivity
  • Enteric Nervous System / physiology
  • Immunochemistry / methods
  • Intracellular Membranes / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / pharmacology
  • Potassium Chloride / metabolism*
  • Prostaglandins / physiology
  • Receptor, PAR-2
  • Receptors, Thrombin / agonists
  • Receptors, Thrombin / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium / antagonists & inhibitors
  • Sodium / metabolism*
  • Trypsin / pharmacology

Substances

  • Chlorides
  • Oligopeptides
  • Prostaglandins
  • Receptor, PAR-2
  • Receptors, Thrombin
  • seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
  • Bumetanide
  • Barium
  • Potassium Chloride
  • Amiloride
  • Sodium
  • Trypsin