Prostaglandins reduce hydrochloric acid-induced increase in duodenal mucosal permeability by a mechanism not related to stimulation of alkaline secretion.
The aim was to investigate whether prostaglandins affect HCl-induced mucosal permeability and to elucidate the role of mucosal bicarbonate secretion in protection. Proximal duodenum of anaesthetized rats were perfused with hydrochloric acid and the effects on luminal alkalinization, mucosal permeability and morphology examined in the absence and in the presence of prostaglandin E2 and/or indomethacin. Luminal alkalinization was determined by back titration of the perfusate and mucosal permeability assessed by measuring the clearance of 51Cr-labelled ethylenediaminetetraacetat ([51Cr]EDTA) from blood-to-intestinal lumen. Perfusion with 100 mM HCl for 5 min increased mucosal permeability sixfold and caused villus tip damage. Luminal administration of PGE2 at a concentration of 10(-6) M had no effect whereas 10(-4) M increased alkalinization by 100% but neither concentration affected the HCl-induced increase in mucosal permeability. PGE2 (10(-4) M), however, improved the ability of the duodenal mucosa to recover from the HCl-induced increase in mucosal permeability. Indomethacin (5 mg kg-1, i.v.) increased alkalinization, augmented HCl-induced mucosal permeability and aggravated mucosal injury. In animals pre-treated with PGE2 plus indomethacin, the HCl-induced increases in mucosal permeability were lower and injury less pronounced than in animals treated with indomethacin alone. No correlation was found between the rate of alkalinization and the HCl-induced increase in mucosal permeability. It is concluded that endogenous prostaglandins reduced the extent of 100 mM HCl-induced duodenal mucosal damage by a mechanism other than the stimulation of alkaline secretion.
Nylander
O
O
Department of Physiology, Uppsala University, Sweden.
Andersson
H
H
Wilander
E
E
Sababi
M
M
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002860:Chromium Radioisotopes; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004492:Edetic Acid; D006851:Hydrochloric Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010539:Permeability; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D002860:Chromium Radioisotopes; D011453:Prostaglandins; D004492:Edetic Acid; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin