Effects of methylprednisolone on hydrogen ion absorption in the canine stomach.
The effect of methylprednisolone (2 mg/kg per day given parenterally for 3 doses, 2 wk or 12 wk) on the permeability of mammalian gastric mucosa to hydrogen ion (H(+)) was examined with denervated fundic pouches in dogs with antrectomies. Transmucosal electric potential difference (PD) and net fluxes of H(+) and Na(+) were determined for luminal [H(+)] from 20 to 160 mM and [Na(+)] from 1 to 140 mM ([H(+)] and [Na(+)] were varied reciprocally). The PD was 50-60 mV lumen negative and was constant over the entire range of Na(+) and H(+) concentration tested. Net H(+) flux varied linearly with [H(+)]. Extrapolation indicated apparent H(+) loss at zero luminal concentration, suggesting a basal HCO(3) (-) secretion. Addition of acetylsalicylic acid (ASA) or taurocholate decreased the PD to 30-40 mV and increased threefold the slope of the relation between net H(+) flux and [H(+)] (k(H)). Calculation of PD-independent permeability constants for H(+) (P(H)) with the Goldman constant field equation indicated that this increase in k(H) could not be attributed solely to the associated decrease in PD. Prednisolone administered for 3 doses had no effect on either the basal mucosal permeability to H(+) or the altered permeability induced by ASA or taurocholate. Chronic administration induced a low rate of basal acid secretion (at 12 wk) but had no effect on either PD or k(H). However, the increase in k(H) and P(H) that developed upon addition of ASA or taurocholate in chronically treated dogs was more than one and a half times that of controls. These data suggest that prolonged treatment with glucocorticoids increases susceptibility of the gastric mucosa to damage by agents that increase permeability to H(+).
D000042:Absorption; D000818:Animals; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects; D008775:Methylprednisolone / Q000494:pharmacology*; D010539:Permeability; D012964:Sodium / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D013656:Taurocholic Acid; D012964:Sodium; D001241:Aspirin; D008775:Methylprednisolone