title: In vitro protection of amphibian gastric mucosa by nutrient HCO3- against aspirin injury.
abstract: The effects of luminal aspirin [acetylsalicylic acid (ASA)] at luminal pH 4.5 and pH 3.0 on Ussing chambered amphibian gastric fundic and antral mucosae were investigated using different concentrations of HCO3- ([HCO3-]) in the nutrient solution in histamine-stimulated or metiamide-treated tissues. The severe surface cell and oxyntic gland injury seen in histamine-stimulated tissues after a 3-h exposure to 20 mM ASA at luminal pH 4.5 in HCO3- -free nutrient solution (HEPES) was prevented by including 18 mM or 48 mM HCO3- in the nutrient solution. At luminal pH 3.0, 48 mM HCO3- in the nutrient solution delayed the histologic damage to the surface epithelium and oxyntic glands caused by a 30-min exposure to 20 mM luminal ASA, but it afforded no protection to a 60-min exposure. This protection of the gastric epithelium by a high nutrient [HCO3-] did not occur in metiamide-treated tissues at luminal pH 3.0. Although the injury to antral epithelial cells exposed to 20 mM luminal ASA at luminal pH 3.0 or 4.5 was less severe than that in fundic mucosae, 48 mM HCO3- in the nutrient solution also afforded clear protection in this tissue. A high nutrient [HCO3-] prevented the sharp fall in the potential difference observed in fundus exposed to ASA at luminal pH 4.5 and delayed the fall in potential difference observed in fundic and antral mucosae exposed to ASA at luminal pH 3.0. The high nutrient [HCO3-] did not prevent the increase in resistance observed in tissues during ASA exposure at luminal pH 4.5 and 3.0. The electrical data reflect not only the damaged surface and oxyntic cells caused by ASA, but also the complex effects of ASA on active and passive ion transport. We conclude the following: (a) The mucosal injury to the fundus and antrum caused by luminal ASA is prevented by 48 mM HCO3- in the nutrient solution when luminal pH is 3.0 and by 18 mM HCO3- when luminal pH is 4.5. Absence of nutrient HCO3- accentuates the injury caused by luminal ASA. (b) The luminal pH, concentration, and time of exposure influence the depth and severity of ASA injury to the fundic and antral mucosa. (c) The electrophysiologic and morphologic changes after ASA exposure are not interrelated, due to the complex effects of ASA on the ion transport and morphology of the gastric epithelium.
mesh_terms: D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D001639:Bicarbonates / Q000494:pharmacology*; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects; D005748:Gastric Fundus / Q000187:drug effects / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008785:Metiamide / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000473:pathology; D011892:Rana catesbeiana
chemical_list: D001639:Bicarbonates; D008785:Metiamide; D006632:Histamine; D001241:Aspirin