The association between PGE2 activity and mucosal permeability in proximal small bowel.
Little is known about the ontogeny of cyclooxygenase activity and synthesis of prostaglandins in the developing gastrointestinal tract. We tested the hypothesis that an age-related increase in cyclooxygenase as reflected in production of PGE2 in the proximal small bowel (PSB) is associated with the maturation of the mucosal barrier as determined by 51Cr-EDTA permeability. Cyclooxygenase activity in PSB of rats at 10, 22, 36, and 63 (adult) days of age was determined by the generation of PGE2 using specific radioimmunoassay. Systemic 51Cr-EDTA clearance into the lumen was used to assess mucosal barrier function in PSB in 10- to 12-day-old and adult rats. Prostaglandin E2 generation rose significantly from 24.8 +/- 0.4 pg/mg/min in 10-day-old rats to 125.0 +/- 7.8 in adult rats. The 51Cr-EDTA clearance decreased significantly 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 endogenous PGE2 in directly mediating these observed changes in the mucosal permeability, a group of adult rats chronically received indomethacin (2.5 mg/kg/day) over a 3-day period, while another group of vehicle-treated rats served as controls. The 51Cr-EDTA clearance of the indomethacin-treated rats was significantly higher than the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of General Surgery, Milton S. Hershey Medical Center, Penn State University, Hershey, Pennsylvania 17033.
J T
JT
Gerstle
J
J
Seaton
G L
GL
Kauffman
P C
PC
Colony
D000375:Aging / Q000502:physiology; D000818:Animals; D002463:Cell Membrane Permeability; D002860:Chromium Radioisotopes; D015232:Dinoprostone / Q000378:metabolism*; D004492:Edetic Acid / Q000493:pharmacokinetics; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D002860:Chromium Radioisotopes; D004492:Edetic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin