Antisecretory effect of leminoprazole on histamine-stimulated gastric acid secretion in dogs: potent local effect.
ABSTRACT Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for > 26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8-10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.
- SourceAvailable from: Susumu Okabe[Show abstract] [Hide abstract]
ABSTRACT: To examine the effects of beer, ethanol, peptone meal and combinations of either peptone meal and beer or peptone meal and ethanol on gastric acid secretion in vagally denervated pouch dogs. The oral administration of either 200 mL of beer, 5% ethanol or 10% peptone meal significantly stimulated gastric acid secretion for 60-90 min in these dogs. With 5% ethanol the plasma gastrin concentration was not affected for 90 min. Combinations of 10% peptone and beer (peptone-beer) or 10% peptone and 5% ethanol (peptone-ethanol) potentiated the acid secretion and increased the plasma gastrin level. While a selective cholecystokinin-B/gastrin receptor antagonist, S-0509, had no effect on ethanol-stimulated acid secretion, the compound markedly inhibited both peptone-beer-stimulated and peptone-ethanol-stimulated gastric acid secretion. Famotidine and atropine significantly inhibited gastric acid secretion stimulated by 5% ethanol, peptone-beer and peptone-ethanol. The mechanisms by which peptone-beer and peptone-ethanol stimulate gastric acid secretion may be mediated not only by increased plasma gastrin, but also by the action of histamine and acetylcholine coupled with the increased plasma gastrin. Ethanol-stimulated secretion appears to be unrelated to circulating gastrin, yet may be related to the acid regulatory mechanism involving histamine and acetylcholine.Alimentary Pharmacology & Therapeutics 05/2000; 14 Suppl 1:109-15. · 4.55 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown. To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants. Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer. In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion. S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion.Alimentary Pharmacology & Therapeutics 05/2000; 14(4):479-88. · 4.55 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: 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.Pharmacology 08/1998; 57(1):47-56. · 1.60 Impact Factor