Relationship between lesion formation and permeability of rat gastric mucosa to H+ and other cations.
The relationship between lesion formation and ionic permeability has been investigated in rat gastric mucosa in vivo. Changes in these parameters were measured in the mucosa treated topically with prostaglandins E2 and A2 and/or aspirin. Particular attention was paid to the net flux of H+ ions across the gastric mucosa. The effect of aspirin concentrations of 5 mM, 20 mM and '40 mM' (the latter, a suspension in a saturated solution) was investigated. Aspirin concentrations of 20 mM and '40 mM' produced a marked increase in lesion formation and increased the net mucosal to serosal flux of H+ ions. Aspirin 5 mM produced a significant increase in lesion formation but did not cause a significant change in net H+ ion flux. This result suggests that aspirin can have a direct irritant effect on the gastric mucosa and that the back diffusion of H+ ions is not a pre-requisite for the development of overt mucosal ulceration. The effect of topically applied prostaglandin E2 (PGE2) on aspirin-induced gastric mucosal damage was investigated. Concentrations of PGE2 of 10(-5) M and 10(-4) M ameliorated aspirin-induced damage, but these changes were not necessarily accompanied by a significant reduction in net H+ ion flux. Again, this result is not consistent with a direct relationship between lesion formation and mucosal permeability to H+ ions. Since PGA2 did not ameliorate aspirin-induced mucosal damage, the protective effect of PGE2 could not be attributed to its conversion to PGA2 in the acidic environment of the gastric lumen. 5 Changes in gastric mucosal potential difference (p.d.) and net fluxes of Na+ and K+ ions may occur without a concomitant change in the permeability of the gastric mucosa to acid back-diffusion. Thus, the assumption cannot be made that a change in the permeability of the gastric mucosa to one particular ion reflects a general increase in ionic permeability.
D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D011454:Prostaglandins A / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced*
D011454:Prostaglandins A; D011458:Prostaglandins E; D006859:Hydrogen; D012964:Sodium; C100008:prostaglandin A2; D015232:Dinoprostone; D001241:Aspirin; D011188:Potassium