Effect of simulated systemic administration of aspirin, salicylate, and indomethacin on amphibian gastric mucosa.
The effects of 20 mM aspirin (ASA), 20 mM sodium salicylate (SA), or 10(-4) M indomethacin placed in the nutrient solution (N) to stimulate systemic administration were investigated at pHN 7.3 in Ussing-chambered amphibian gastric mucosae. In histamine-stimulated tissues, the initial rise and subsequent rapid fall in potential difference, rise in resistance, and inhibition of hydrogen ion (H+) secretion induced by SAN did not occur with ASAN unless hydrolysis of ASAN produced a SAN of greater than 3 mM. In metiamide-treated tissues, 20 mM SAN caused an immediate fall in potential difference and an increase in resistance; 2 mM SAN and 20 mM ASA produced similar qualitative electrical changes, but only those induced by ASA were reversible. IndomethacinN caused no significant changes in potential difference, resistance, or H+ secretion in histamine- or metiamide-treated tissues. Despite producing highly significant reductions in generation of prostaglandin E2, and prostaglanndin F2 alpha and 6-keto prostaglandin F1 alpha, ASAN and indomethacin caused no surface ulceration. Sodium salicylate placed in the nutrient solution caused only a small reduction in prostaglandin F2 alpha, without change in the other prostaglandins, and produced extensive edema in the lamina propria, histologically. We conclude the following: (a) The inhibition of H+ secretion and electrical changes caused by SAN in histamine-treated gastric fundus are not observed with ASAN unless there is hydrolysis to [SAN] greater than 3 mM. (b) Our data strongly implicate the SAN in ASAN-containing solutions as being responsible for the electrical effects and inhibition of H+ secretion. (c) There is no correlation in vitro between inhibition of prostaglandin synthesis and the electrical or morphologic changes produced by nutrient exposure to ASA, SA, or indomethacin.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D004594:Electrophysiology / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology*; D008785:Metiamide / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D011892:Rana catesbeiana; D012980:Sodium Salicylate / Q000494:pharmacology*; D013997:Time Factors
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D008785:Metiamide; D015121:6-Ketoprostaglandin F1 alpha; D006632:Histamine; D015237:Dinoprost; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D001241:Aspirin; D012980:Sodium Salicylate; D007213:Indomethacin