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

Abstract

. Prostaglandinmediated inhibition of Na ϩ /H ϩ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine. Am J Physiol Gastrointest Liver Physiol 291: G885-G894, 2006. First published March 30, 2006 doi:10.1152/ajpgi.00380.2005.-Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl Ϫ secretion and inhibition of electroneutral Na ϩ /H ϩ 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 22 Na 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 Ͻ 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 M) 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 M) or serosal cariporide (25 M), respectively, had no effect. Ischemiainjured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22 Na ϩ (by ϳ35%) compared with nontreated ischemia-injured control tissues (P Ͻ 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.

Ischemia and reperfusion of rat small intestine using pentoxyfilline and prostaglandin E1

“…After histological analysis according Chiu et al 20 it was demonstrated that without PTX 1,13,14,16 and PGE1 [17][18][19][20] The PGE1 [17][18][19], is known by its intense vasodilator effect, for being a substance with intense biological activity that has been used for such a longtime to treat. the chronic arterial occlusive disease, since beside to vasodilation capacity it also inhibit platelets aggregation.…”

“…PGE1 has a role in the activation of fibrinolysis and/ or fibrogenesis, in the modulation of cellular proliferation, in the hemorreologic activity of erithocytes, in the inhibition and activation of neutrophils capacities and also in the utilization of oxygen and glucose by the tissues. Beside to those effects there is evidence that PGE1 stimulates angiogenesis in cases of myocardic ischemia [17][18][19] .…”

Trefoil Factor 2 Requires Na/H Exchanger 2 Activity to Enhance Mouse Gastric Epithelial Repair

“…There are only a few reports of NHE2 affecting wound repair or cellular migration. Most notably, Blikslager et al (39,40) have shown compelling evidence that genetic elimination of NHE2 weakens recovery of mouse intestinal epithelium after ischemic damage, yet in pig, the pharmacologic inhibition of NHE2 activity strengthens ischemic recovery. The two species manifest qualitatively opposite responses in transepithelial ion permeability after addition of 25 M HOE694, and the basis for these differences remains unresolved.…”

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

“…Further, NHE2 plays a role in mucosal recovery from ischemia reperfusion. Although, whether NHE2 activity is beneficial or detrimental remains to be determined [108,107]. A role for NHE2 in salivation responses has also been observed using the NHE2 KO mice [132].…”