title: Capsaicin-sensitive sensory neurons are involved in bicarbonate secretion induced by lansoprazole, a proton pump inhibitor, in rats.
abstract: Lansoprazole, a proton pump inhibitor, exerts prominent antiulcer activity via both antisecretory and mucosal protective actions. Although the antisecretory action has been explained by inactivation of (H+, K+)-ATPase in parietal cells, the mode of mucosal protective action remains to be elucidated. In the present study, the effect of lansoprazole on duodenal bicarbonate secretion was studied in anesthetized rats to clarify the mode of the mucosal protective action. Lansoprazole (0.1 mM) applied topically to the duodenum significantly (P < 0.01) increased bicarbonate secretion by 0.36 +/- 0.11 microeq/15 min (21 +/- 5%) compared with the value in the vehicle control. Topical administration of capsaicin (10 mg/ml) in the duodenum and intravenous infusion of vasoactive intestinal peptide (10 micrograms/kg/hr) increased bicarbonate secretion. Five-minute perfusion of the duodenal loop with 100 mM HCl increased bicarbonate secretion. Administration of lansoprazole (0.3 and 1 mg/kg, intravenously) 60 min before luminal acidification enhanced the acid-induced bicarbonate secretion dose-dependently and significantly (P < 0.01). In the capsaicin-pretreated rats, the effects of lansoprazole on basal and acid-induced bicarbonate secretion were significantly (P < 0.05) decreased compared with that of control group. These results indicate that lansoprazole increases basal and acid-induced bicarbonate secretion in the duodenum in rats and that capsaicin-sensitive sensory neurons may be involved in the mode of action for these effects.
authors.affiliation: Pharmaceutical Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Inada
authors.forename: H
authors.initials: H
authors.lastname: Satoh
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D015738:Famotidine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D064747:Lansoprazole; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D014660:Vasoactive Intestinal Peptide; D015738:Famotidine; D009853:Omeprazole; D002211:Capsaicin