PROSTAGLANDINS I-2 AND E-2 HAVE A SYNERGISTIC ROLE IN RESCUING EPITHELIAL BARRIER FUNCTION IN PORCINE ILEUM

Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium , possibly because they enhance mucosal repair, The objective of the p resent studies was to assess the role of prostaglandins in intestinal repair, intestinal mucosa from porcine ileum subjected to 1 h of ische mia was mounted in Ussing chambers, Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control, The latter respons e was blocked by inhibition of prostaglandin synthesis, and restored b y addition of both carbacyclin (an analog of PGI(2)) and PGE(2), where as the addition of each alone had little effect. Histologically, prost aglandins had no effect on epithelial restitution of villous contracti on, indicating that elevations in transepithelial resistance were asso ciated with increases in paracellular resistance. Furthermore, prostag landin-stimulated elevations in resistance were inhibited with cytocha lasin D, an agent known to stimulate cytoskeletal contraction. Synergi stic elevations in transepithelial resistance, similar to those of car bacyclin and PGE(2), were also noted after treatment with cAMP and A23 187 (a calcium ionophore). We conclude that PGE(2) and PGI(2) have a s ynergistic role in restoration of intestinal barrier function by incre asing intracellular cAMP and Ca2+, respectively, which in turn signal cytoskeletal-mediated tight junction closure.