THE ASSOCIATION BETWEEN PGE(2) ACTIVITY AND MUCOSAL PERMEABILITY IN PROXIMAL SMALL-BOWEL

Little is known about the ontogeny of cyclooxygenase activity and synt hesis of prostaglandins in the developing gastrointestinal tract. We t ested the hypothesis that an age-related increase in cyclooxygenase as : reflected in production of PGE(2) in the proximal small bowel (PSB) is associated with the maturation of the mucosal barrier as determined by Cr-31-EDTA permeability. Cyclooxygenase activity in PSB of rats at 10, 22, 36, and 63 (adult) days of age was determined by the generati on of PGE, using specific radioimmunoassay. Systemic Cr-51-EDTA cleara nce into the lumen was used to assess mucosal barrier function in PSB in 10- to 12-day-old and adult rats. Prostaglandin E(2) generation ros e significantly from 24.8 +/- 0.4 pg/mg/min in 10-day-old rats to 125. 0 +/- 7.8 in adult rats. The Cr-51-EDTA clearance decreased significan tly from 5.08 +/- 0.90 ml/min/100 g in 10- to 12-day-old rats to 0.43 +/- 0.18 ml/min/100 g in adult rats. To assess the possible role of en dogenous PGE(2) in directly mediating these observed changes in the mu cosal permeability, a group of adult rats chronically received indomet hacin (2.5 mg/kg/day) over a 3-day period, while another group of vehi cle-treated rats served as controls, The Cr-51-EDTA clearance of the i ndomethacin-treated rats was significantly higher than the control rat s. We conclude that (1) PGE(2) activity in PSB rises progressively aft er birth to 36 days of age at which time it plateaus, (2) this increas e in PGE(2) generation with age correlates with a decrease in the perm eability of the PSB mucosal barrier, and (3) the permeability of the P SB mucosal barrier is, in part, mediated through a cyclooxygenase-depe ndent pathway. (C) 1994 Academic Press, Inc.