Influence of prednisolone on gastric alkaline response in rat stomach. A possible explanation for steroid-induced gastric lesion

• Published in: Digestive diseases and sciences 1985-12, Vol.30 (12), p.1166-1173
• Main Authors: NOBUHARA, Y, UEKI, S, TAKEUCHI, K
• Format: Article
• Language: English
• Subjects: 16,16-Dimethylprostaglandin E2 - pharmacology; 6-Ketoprostaglandin F1 alpha - metabolism; Animals; Biological and medical sciences; Cycloheximide - pharmacology; Dinoprostone; Drug toxicity and drugs side effects treatment; Gastric Acid - metabolism; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Hydrogen-Ion Concentration; Male; Medical sciences; Membrane Potentials - drug effects; Perfusion; Pharmacology. Drug treatments; Prednisolone - adverse effects; Prednisolone - antagonists & inhibitors; Prednisolone - pharmacology; Prostaglandins E - metabolism; Rats; Rats, Inbred Strains; Sodium Chloride - metabolism; Stomach Diseases - chemically induced; Toxicity: digestive system
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/BF01314052

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.