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

We have previously shown that PGE(2) enhances recovery of transmucosal resi stance (R) in ischemia-injured porcine ileum via a mechanism involving chlo ride secretion. Because the tyrosine kinase inhibitor genistein amplifies c AMP-induced Cl- secretion, we postulated that genistein would augment PGE(2 )-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 [H-3]N-f ormylmethionyl-leucyl phenylalanine (FMLP) and [H-3]mannitol were monitored as indicators of recovery of barrier function. Treatment with genistein (1 0(-4) M) and PGE(2) (10(-6) M) resulted in synergistic elevations in R and additive reductions in mucosal-to-serosal fluxes of [H-3]FMLP and [H-3]mann itol, whereas treatment with genistein alone had no effect. Treatment of in jured 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 tissu es 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 o f R in the presence of cAMP or cGMP but not in the presence of PKC agonists .