Prostaglandin E2 enhances gastric defense mechanisms against acid injury in uremic rats.
OBJECTIVE
Uremia increases gastric mucosal H+ permeability and acid back-diffusion-related injury in rats. The aim of this study was to examine the effect of the synthetic gastroprotective compound 16,16-dimethyl prostaglandin E2 (16,16-dm PGE2) on the gastric barrier to acid injury in uremic rats.


METHODS
Chronic renal failure was induced by subtotal nephrectomy. Acid back-diffusion injury was induced by superfusion with 15% ethanol in 0.15N HCl and was assessed by image analysis. Intracellular pH, initial surface cell acidification rate, and thickness of mucous gel layer were measured with in vivo microscopy. Gastric mucosal blood flow was measured in separate experiments by laser-Doppler flowmetry.


RESULTS
Pretreatment with 16,16-dm PGE2 attenuated H+ back-diffusion and prevented the production of gross lesions. 16,16-dm PGE2 increased gastric mucous gel thickness, decreased initial acidification rate, and maintained intracellular pH homeostasis during exposure to luminal acid. Gastric mucosal blood flow was not changed during superfusion with a neutral buffer but increased during acid exposure in rats treated with 16,16-dm PGE2.


CONCLUSIONS
16,16-dm PGE2 attenuated H+ back-diffusion injury in uremic rats. This effect was associated with blunting of the initial decrease of intracellular pH and enhanced surface cell intracellular pH homeostasis during acid exposure. These effects were associated with an increased mucous gel layer thickness and an acid-related increase in blood flow.
Nishizaki
Y
Y
Center for Ulcer Research and Education, VA/UCLA Gastroenteric Biology Center.
Guth
P H
PH
Quintero
E
E
Bover
J
J
Del Rivero
M
M
Kaunitz
J D
JD
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D004058:Diffusion; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006851:Hydrochloric Acid / Q000009:adverse effects*; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D009093:Mucus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014511:Uremia / Q000150:complications* / Q000378:metabolism
D006859:Hydrogen; D015064:16,16-Dimethylprostaglandin E2; D006851:Hydrochloric Acid