Mechanism by which orally administered leminoprazole stimulates mucus synthesis in rats.
We examined the mechanism by which leminoprazole (an acid pump inhibitor) stimulates mucus synthesis in rats. Leminoprazole and omeprazole were administered to rats, and then the gastric fragments were isolated from the fundus of their stomachs. Mucus synthesis was assessed by [3H]leucine and [3H]glucosamine incorporation by the fragments into high-molecular-weight materials. After oral administration of leminoprazole, mucus synthesis by the gastric fragments was dose-dependently stimulated, while acid secretion was inhibited. Omeprazole had no effect on mucus synthesis, although it potently inhibited acid secretion. Treatment with NG-nitro-L-arginine methyl ester (L-NAME), but not indomethacin, caused a reduction of leminoprazole-stimulated synthesis of gastric mucus in a dose-dependent manner. The inhibitory action of L-NAME was restored by the concomitant administration of L-arginine, but not D-arginine. Intragastric administration of leminoprazole to pylorus-ligated rats also stimulated mucus synthesis without inhibiting acid secretion. In contrast, in the case of intraperitoneal administration, leminoprazole exerted a potent antisecretory effect, but failed to promote mucus synthesis. Exposure of leminoprazole to the luminal surface of the gastric mucosa did not cause any damage. We conclude that orally administered leminoprazole, via direct effect toward the gastric mucosa, stimulates mucus synthesis in rats probably through nitric oxide mediation. The stimulatory effect of leminoprazole on mucus synthesis is independent of its antisecretory effect.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D008297:Male; D009093:Mucus / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D018722:Nicotinic Agonists; C089751:leminoprazole; D002217:Carbachol; D015064:16,16-Dimethylprostaglandin E2; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin