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Departments of 1 Clinical Sciences, 2 Food Animal Health and Resource Management, and 3 Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, 27606; and 4 Department of Pediatrics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599.
We have previously shown that PGE2 enhances
recovery of transmucosal resistance (R) in
ischemia-injured porcine ileum via a mechanism involving
chloride secretion. Because the tyrosine kinase inhibitor genistein
amplifies cAMP-induced Cl
secretion, we postulated
that genistein would augment PGE2-induced recovery of
R. Porcine ileum subjected to 45 min of ischemia was mounted in Ussing chambers, and R and mucosal-to-serosal fluxes of [3H]N-formyl-methionyl-leucyl
phenylalanine (FMLP) and [3H]mannitol were
monitored as indicators of recovery of barrier function. Treatment with
genistein (10
4 M) and PGE2
(10
6 M) resulted in synergistic
elevations in R and additive reductions in mucosal-to-serosal
fluxes of [3H]FMLP and
[3H]mannitol, whereas treatment with genistein
alone had no effect. Treatment of injured tissues with genistein and
either 8-bromo-cAMP (10
4 M) or cGMP
(10
4 M) resulted in synergistic
increases in R. However, treatment of tissues with genistein
and the protein kinase C (PKC) agonist phorbol myristate acetate
(10
5-10
6
M) had no effect on R. Genistein augments recovery of R
in the presence of cAMP or cGMP but not in the presence of PKC agonists.
mucosa; chloride secretion; transmucosal resistance; tyrosine kinase
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