Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine

Adam J. Moeser, Prashant K. Nighot, Kathleen A. Ryan, Jenna G. Wooten, Anthony T. Blikslager

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl- secretion and inhibition of electroneutral Na+/H+ exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current (Isc), transepithelial electrical resistance (TER), and isotopic fluxes of 22Na were measured in response to PGE2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER (P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 μM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in Isc and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 μM) or serosal cariporide (25 μM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22Na+ (by ∼35%) compared with nontreated ischemia-injured control tissues (P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.

Original languageEnglish (US)
Pages (from-to)G885-G894
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume291
Issue number5
DOIs
StatePublished - Nov 1 2006

Fingerprint

Sodium-Hydrogen Antiporter
Recovery of Function
Prostaglandins
Intestines
Protein Isoforms
Ischemia
3-(2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methylphenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride
Electric Impedance
Ileum
Swine
Immunoassay
Dinoprostone
Mucous Membrane
Pharmacology

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

@article{55a02ac523db4d2e9f652c2db7cb0ac5,
title = "Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine",
abstract = "Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl- secretion and inhibition of electroneutral Na+/H+ exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current (Isc), transepithelial electrical resistance (TER), and isotopic fluxes of 22Na were measured in response to PGE2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45{\%} reduction in TER (P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 μM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in Isc and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 μM) or serosal cariporide (25 μM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22Na+ (by ∼35{\%}) compared with nontreated ischemia-injured control tissues (P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.",
author = "Moeser, {Adam J.} and Nighot, {Prashant K.} and Ryan, {Kathleen A.} and Wooten, {Jenna G.} and Blikslager, {Anthony T.}",
year = "2006",
month = "11",
day = "1",
doi = "10.1152/ajpgi.00380.2005",
language = "English (US)",
volume = "291",
pages = "G885--G894",
journal = "American Journal of Physiology",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "5",

}

Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine. / Moeser, Adam J.; Nighot, Prashant K.; Ryan, Kathleen A.; Wooten, Jenna G.; Blikslager, Anthony T.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 291, No. 5, 01.11.2006, p. G885-G894.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine

AU - Moeser, Adam J.

AU - Nighot, Prashant K.

AU - Ryan, Kathleen A.

AU - Wooten, Jenna G.

AU - Blikslager, Anthony T.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl- secretion and inhibition of electroneutral Na+/H+ exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current (Isc), transepithelial electrical resistance (TER), and isotopic fluxes of 22Na were measured in response to PGE2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER (P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 μM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in Isc and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 μM) or serosal cariporide (25 μM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22Na+ (by ∼35%) compared with nontreated ischemia-injured control tissues (P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.

AB - Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl- secretion and inhibition of electroneutral Na+/H+ exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current (Isc), transepithelial electrical resistance (TER), and isotopic fluxes of 22Na were measured in response to PGE2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER (P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 μM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in Isc and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 μM) or serosal cariporide (25 μM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22Na+ (by ∼35%) compared with nontreated ischemia-injured control tissues (P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.

UR - http://www.scopus.com/inward/record.url?scp=33751118010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751118010&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00380.2005

DO - 10.1152/ajpgi.00380.2005

M3 - Article

C2 - 16574991

AN - SCOPUS:33751118010

VL - 291

SP - G885-G894

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1849

IS - 5

ER -