Effects of antiinflammatory agents and prostaglandins on acid and bicarbonate secretions in the amphibian-isolated gastric mucosa.
Effects of antiinflammatory agents and prostaglandins on H+ and HCO-3 secretions and electrical properties were investigated in the amphibian-isolated gastric mucosa. Gastric HCO-3 transport was studied in Rana temporaria fundus, in which H+ secretion had been inhibited with the histamine H2-receptor antagonists metiamide or cimetidine (10(-3) M), and in Necturus antrum, which secreted HCO-3 spontaneously. Hydrocortisone (100-500 microgram/ml) had no effect on H+ or HCO-3 secretion in the fundus. Indomethacin (10(-4) M) was a considerably more potent inhibitor of HCO-3 secretion than of H+ secretion in the fundus and also inhibited HCO-3 transport in the antrum. Fenclofenac (3 x 10(-3) M) almost abolished fundic HCO-3 transport and also depressed H+ secretion. There was a marked fall in transmucosal potential difference and a decrease in electrical resistance in fenclofenac-treated mucosae whereas indomethacin had less effect on electrical properties at the concentrations used here. The prostaglandins, E2, 16,16-dimethyl E2 and I2 all inhibited H+ secretion but only 16,16-dimethyl E2 stimulated HCO-3 secretion. The inhibitory action of indomethacin on HCO-3 secretion was prevented by co-administration of 16,16-dimethyl PGE2 (10(-6) M). It is proposed that the inhibitory action of nonsteroidal antiinflammatory drugs and the stimulatory action of some prostaglandins on HCO-3 secretion contributes to their ulcerogenic and anti-ulcer actions on the gastric mucosa.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001001:Anura; D001639:Bicarbonates / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008785:Metiamide / Q000494:pharmacology; D010647:Phenyl Ethers / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D011896:Rana temporaria; D012636:Secretory Rate / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D001639:Bicarbonates; D010647:Phenyl Ethers; D010648:Phenylacetates; D011465:Prostaglandins, Synthetic; D008785:Metiamide; D002927:Cimetidine; D006854:Hydrocortisone; D007213:Indomethacin; C012970:fenclofenac