Effects of Isoprostanes and Prostanoids on Porcine Small Intestine

The isoprostanes are prostaglandin (PG)-like compounds formed in vivo by free-radical-catalyzed peroxidation of polyunsaturated fatty acids and are synthesized independent of cyclooxygenase. It has been debated whether the biological effects of the isoprostanes are exerted on prostanoid receptors [thromboxane A2 (TP) receptors and prostanoid E (EP) receptors] or on a "unique" isoprostane receptor. We sought to define the receptors involved in the actions of isoprostanes on the porcine small intestine. Stripped intestinal sheets were mounted in Ussing chambers, and bioelectrical parameters were recorded. Serosal application of 8-iso-PGE2 (pEC(50) = 5.71), PGE2 (pEC(50) = 6.45 and pEC(50) = 5.04), and PGF2alpha (pEC(50) = 5.07) elicited concentration-dependent increases in the short-circuit current (I(SC)). No responses were seen with 8-iso-PGF2alpha. The TP receptor agonist U46619 induced transient increase in I(SC), and the tissue responded to a further challenge to PGE2. Pretreatment with U46619 did not alter responses to a subsequent addition of either PGE2 or 8-iso-PGE2. The TP receptor antagonist SQ29,548 significantly reduced responses to the TP agonist, U46619, but did not antagonize responses to 8-iso-PGE2. Homologous and heterologous desensitization between 8-iso-PGE2, PGE2, and PGF2alpha suggested the involvement of prostanoid EP and prostanoid F (FP) receptors in the response elicited to 8-iso-PGE2. The effects of 8-iso-PGE2 were not inhibited by tetrodotoxin. Pretreatment of the tissues with bumetanide significantly reduced the increase in I(SC). The results indicate that 8-iso-PGE2 induces a Cl- secretion, and the effects involve prostanoid EP and FP receptors but not TP receptors in the porcine small intestine.