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Am J Physiol Gastrointest Liver Physiol 278: G207-G216, 2000;
0193-1857/00 $5.00
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Vol. 278, Issue 2, G207-G216, February 2000

Genistein augments prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum

Anthony T. Blikslager1, Malcolm C. Roberts2, Karen M. Young1, J. Marc Rhoads4, and Robert A. Argenzio3

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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