title: Influence of prednisolone on gastric alkaline response in rat stomach. A possible explanation for steroid-induced gastric lesion.
abstract: Exposure of the rat stomach for 10 min to 1 M NaCl produced an increase of luminal pH (alkaline response) with a concomitant reduction of the transmucosal potential difference (PD) and an increased generation of mucosal prostaglandins of E2 and 6-keto F1 alpha. Prednisolone (3-50 mg/kg), given subcutaneously 4 hr before exposure to 1 M NaCl, dose-dependently inhibited alkaline response without affecting the PD reduction, and at 50 mg/kg completely prevented the increased production of mucosal prostaglandins after exposure to 1 M NaCl. The inhibitory effect of prednisolone on alkaline response was significantly antagonized by pretreatment with 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) (3 micrograms/kg) or cycloheximide (1.5 mg/kg). A repeated administration of prednisolone (3-50 mg/kg), once daily for 4 days, produced gastric lesions dose-dependently. At 50 mg/kg, gastric lesions appeared after administration of this drug for more than 2 days, and the inhibition of alkaline response caused by 1 M NaCl became more potent as the days of treatment increased. Either 16,16-dmPGE2 (10-100 micrograms/kg) or cycloheximide (1 or 3 mg/kg), given daily in two divided doses for 4 days, dose-dependently inhibited formation of gastric lesions in response to prednisolone (50 mg/kg). These results indicate that prednisolone inhibits gastric alkaline response caused by 1 M NaCl by reducing generation of endogenous prostaglandins. The weakened self-defense mechanisms caused by prednisolone may be involved in the pathogenesis of steroid-induced gastric lesions.
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010477:Perfusion; D011239:Prednisolone / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000378:metabolism; D013272:Stomach Diseases / Q000139:chemically induced*
chemical_list: D011458:Prostaglandins E; D012965:Sodium Chloride; D015121:6-Ketoprostaglandin F1 alpha; D003513:Cycloheximide; D011239:Prednisolone; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2