Genistein augments prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum.
We have previously shown that PGE(2) 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 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 [(3)H]N-formyl-methionyl-leucyl phenylalanine (FMLP) and [(3)H]mannitol were monitored as indicators of recovery of barrier function. Treatment with genistein (10(-4) M) and PGE(2) (10(-6) M) resulted in synergistic elevations in R and additive reductions in mucosal-to-serosal fluxes of [(3)H]FMLP and [(3)H]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.
Blikslager
A T
AT
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, 27606, North Carolina. anthony@blikslager@ncsu.edu
Roberts
M C
MC
Young
K M
KM
Rhoads
J M
JM
Argenzio
R A
RA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D017097:Electric Impedance; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D007082:Ileum / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D013552:Swine / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D002712:Chlorides; D014316:Tritium; D015124:8-Bromo Cyclic Adenosine Monophosphate; D008353:Mannitol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019833:Genistein; D006152:Cyclic GMP; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate