Role of prostaglandins in maintaining gastric mucus-cell permeability against acid exposure.
Regulation of gastric epithelial permeability is important in the protection of the gastric mucosa from secreted acid. However, the mechanism(s) for this regulation in gastric mucus cells remains unknown. In this study, we evaluated gastric epithelial-cell permeability in response to acid exposure by monitoring trans-epithelial electrical resistance (TEER) and paracellular permeability with carbon 14-labeled mannitol. We also examined the role of prostaglandins on gastric epithelial permeability. Rat gastric epithelial cells (RGM-1) were plated on 8-microm-pore tissue-culture inserts. Cells were exposed to solutions of differing pH (3-7.4), with and without the nonsteroidal antiinflammatory drug (NSAID) indomethacin (10(-7) mol/L), for 60 to 120 minutes. Transepithelial permeability was measured on the basis of TEER and the diffusion rate of [(14)C]mannitol. Prostaglandin E(2) (PGE(2)) was administered in some experiments with NSAIDs. After acid exposure (pH 3.0-5.0), TEER rapidly and significantly increased, peaking in 5 minutes. Diffusion of [(14)C]mannitol was blocked during the period when TEER increased. Pretreatment with the cyclooxygenase (COX) inhibitor indomethacin blocked the rapid acid-induced increase in TEER. A specific COX-2 inhibitor had no effect on this rapid increase in TEER. The blockade by indomethacin was eliminated by the addition of PGE(2). These findings suggest that when gastric-surface mucus cells are exposed to acid, gastric epithelial permeability decreases rapidly to inhibit acid back-diffusion. Prostaglandins play an important role in this protective response to acid exposure. COX inhibitors such as indomethacin may inhibit the regulation of epithelial permeability by reducing the concentration of PGE(2).
Takezono
Yasuhide
Y
Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Joh
Takashi
T
Oshima
Tadayuki
T
Suzuki
Hideo
H
Seno
Kyoji
K
Yokoyama
Yoshifumi
Y
Alexander
J Steven
JS
Itoh
Makoto
M
D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004058:Diffusion; D015232:Dinoprostone / Q000494:pharmacology; D004338:Drug Combinations; D004594:Electrophysiology; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006851:Hydrochloric Acid / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
D004338:Drug Combinations; D011453:Prostaglandins; D008353:Mannitol; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin