The association between PGE2 activity and mucosal permeability in proximal small bowel

J T Gerstle1, J Seaton, G L Kauffman

  • 1Division of General Surgery, Milton S. Hershey Medical Center, Penn State University, Hershey, Pennsylvania 17033.

Insights

Prostaglandin E2 production and cyclooxygenase activity increase with age in the developing rat gut, correlating with improved mucosal barrier function. Inhibiting prostaglandin synthesis in adult rats increased gut permeability.

Area of Science:

  • Gastroenterology
  • Developmental Biology
  • Pharmacology

Background:

  • The ontogeny of cyclooxygenase (COX) activity and prostaglandin synthesis in the developing gastrointestinal tract is not well understood.
  • Prostaglandins play crucial roles in maintaining gastrointestinal mucosal integrity.

Purpose of the Study:

  • To investigate the age-related changes in cyclooxygenase activity and prostaglandin E2 (PGE2) production in the developing rat proximal small bowel (PSB).
  • To determine the association between increased PGE2 production and the maturation of the mucosal barrier function.
  • To assess the role of endogenous PGE2 in mediating mucosal barrier integrity.

Main Methods:

  • Cyclooxygenase activity was measured by PGE2 generation using radioimmunoassay in rats at 10, 22, 36, and 63 days of age.
  • Mucosal barrier function in the PSB was assessed using 51Cr-EDTA clearance in 10- to 12-day-old and adult rats.
  • The effect of indomethacin (a COX inhibitor) on mucosal permeability was evaluated in adult rats.

Main Results:

  • PGE2 generation in the PSB significantly increased with age, from 24.8 pg/mg/min in 10-day-old rats to 125.0 pg/mg/min in adult rats.
  • 51Cr-EDTA clearance, indicating mucosal permeability, significantly decreased with age, from 5.08 ml/min/100 g in young rats to 0.43 ml/min/100 g in adult rats.
  • Indomethacin treatment in adult rats significantly increased 51Cr-EDTA clearance, indicating heightened mucosal permeability.

Conclusions:

  • There is an age-related increase in cyclooxygenase activity and PGE2 production in the developing rat proximal small bowel.
  • Maturation of the gastrointestinal mucosal barrier is associated with increased PGE2 synthesis.
  • Endogenous prostaglandins, particularly PGE2, play a significant role in maintaining mucosal barrier function in the adult rat gastrointestinal tract.

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