Effect of cyclooxygenase inhibition on macromolecular transport in rat gastric mucosa.
We have shown that the rat gastric mucosa takes up antigenically intact protein in vitro. The present study investigated the effect of two cyclooxygenase inhibitors, indomethacin and piroxicam, on gastric transport of BSA. Fasted rats were given indomethacin, piroxicam, or vehicle. After 30 min, the stomach was removed, stripped, and mounted in a Ussing chamber. Each side was bathed with Krebs buffer. Bovine serum albumin (BSA), 125I-labeled BSA (125I-BSA), and 51Cr-labeled EDTA (51Cr-EDTA) were added to the mucosal fluid and equilibrated for 30 min. Serosal fluids were sampled for two subsequent 30-min periods, and mean fluxes for immunologically intact BSA (enzyme-linked immunoabsorbent assay), total BSA (125I-BSA), and 51Cr-EDTA were calculated. Cyclooxygenase inhibition significantly (P < 0.01) reduced tissue prostaglandin E2 synthetic capacity (indomethacin, 97%; piroxicam, 92%) but did not cause either macroscopic or microscopic mucosal injury. Both inhibitors significantly (P < 0.05) decreased uptake of immunologically intact BSA (indomethacin, 91%; piroxicam, 81%) and 51Cr-EDTA. In contrast, the movement of degraded BSA was not altered by indomethacin. These findings suggest that a selective pathway exists for the uptake of intact proteins in gastric mucosa and that the pathway is modulated by cyclooxygenase metabolites.
Curtis
G H
GH
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
MacNaughton
W K
WK
Gall
D G
DG
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002860:Chromium Radioisotopes; D015232:Dinoprostone / Q000378:metabolism; D004492:Edetic Acid; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D010539:Permeability; D010894:Piroxicam / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000502:physiology
D002860:Chromium Radioisotopes; D007457:Iodine Radioisotopes; D010894:Piroxicam; D012710:Serum Albumin, Bovine; D012969:Sodium Fluoride; D004492:Edetic Acid; D015232:Dinoprostone; D007213:Indomethacin