Abstract
Lansoprazole, a proton pump inhibitor, exerts prominent antiulcer activityvia 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 μeq/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 μg/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.
Similar content being viewed by others
References
Wallace JL, Bell CJ: Gastroduodenal mucosal defense. Curr Opin Gastroenterol 9:902–908, 1993
Isenberg JI, Smedfors B, Johansson C: Effect of graded doses of intraluminal H+, prostaglandin E2, and inhibition of endogenous prostaglandin synthesis on proximal duodenal bicarbonate secretion in unanesthetized rat. Gastroenterology 88:303–307, 1985
Takeuchi K, Matsumoto J, Ueshima K, Okabe S: Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum. Gastroenterology 101:954–961, 1991
Scheiman JM, Kraus ER, Boland CR: Regulation of canine gastric mucin synthesis and phospholipid secretion by acid secretagogues. Gastroenterology 103:1842–1850, 1992
Matsumoto J, Takeuchi K, Ueshima K, Okabe S: Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants. Dig Dis Sci 37:1336–1344, 1992
Feil W, Klimesch S, Karner P, Wenzi E, Starlinger M, Lacy ER, Schiessel R: Importance of an alkaline microenvironment for rapid restitution of the rabbit duodenal mucosain vitro. Gastroenterology 97:112–122, 1989
Silen W: Leakage of HCO3 and mucosal restitution. J Int Med 228(suppl 1):59–62, 1990
Ballesteros MA, Wolosin JD, Hogan DL, Koss MA, Isenberg JI: Cholinergic regulation of human proximal duodenal mucosal bicarbonate secretion. Am J Physiol 261:G327-G331, 1991
Flemström G, Säfsten B: Role of dopamine and other stimuli of mucosal bicarbonate secretion in duodenal protection. Dig Dis Sci 39:1839–1842, 1994
Flemström G, Heylings JR, Garner A: Gastric and duodenal HCO3 transportin vitro: Effects of hormones and local transmitters. Am J Physiol 242:G100-G110, 1982
Buck SH, Burks TF: The neuropharmacology of capsaicin: Review of some recent observations. Pharmacol Rev 38:179–226, 1986
Holzer P, Pabst MA, Lippe IT, Peskar BM, Peskar BA, Livingston EH, Guth PH: Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology 98:838–848, 1990
Satoh H, Inatomi N, Nagaya H, Inada I, Nohara A, Nakamura N, Maki Y: Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats. J Pharmacol Exp Ther 248:806–815, 1989
Inatomi N, Nagaya H, Takami K, Shino A, Satoh H: Effects of a proton pump inhibitor, AG-1749 (lansoprazole), on reflux esophagitis and experimental ulcers in rats. Jpn J Pharmacol 55:437–451, 1991
Isenberg JI, Selling JA, Hogan DL, Koss MA: Impaired proximal duodenal mucosal bicarbonate secretion in patients with duodenal ulcer. N Engl J Med 316:374–379, 1987
Bukhave K, Rask-Madsen J, Hogan DL, Koss MA, Isenberg JI: Proximal duodenal prostaglandin E2 release and mucosal bicarbonate secretion are altered in patients with duodenal ulcer. Gastroenterology 99:951–955, 1990
Mertz-Nielsen A, Hillingso J, Eskerod O, Frøkier H, Bukhave K, Rask-Madsen J: Evidence for increased gastric PGE2 release and bicarbonate output secondary to a defective duodenal mucosal bicarbonate secretion in patients with duodenal ulcer. Gastroenterology 104:A-146, 1993 (abstract)
Holzer P, Sametz W: Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 91:975–981, 1986
Maggi CA, Evangelista S, Abelli L, Somma V, Meli A: Capsaicin-sensitive mechanisms and experimentally induced duodenal ulcers in rats. J Pharm Pharmacol 39:559–561, 1987
Takeuchi K, Matsumoto J, Ueshima K, Ohuchi T, Okabe S: Induction of duodenal ulcers in sensory deafferented rats following histamine infusion. Digestion 51:203–210, 1992
Takeuchi K, Ueshima K, Ohuchi T, Okabe S: The role of capsaicin-sensitive sensory neurons in healing of HCl-induced gastric mucosal lesions in rats. Gastroenterology 106:1524–1532, 1994
Smedfors B, Theodorsson E, Aly A, Musat A, Panja AB, Johansson C: HCl-induced duodenal HCO3 − secretion is associated with concentration related release of local prostaglandin E2, vasoactive intestinal peptide, neurokinin A and substance P in the rat. Eur J Gastroenterol Hepatol 1:193–199, 1989
Algazi MC, Chen H-S, Koss MA, Hogan DL, Steinbach J, Pandol SJ, Isenberg JI: Effect of VIP antagonist on VIP-, PGE2-, and acid-stimulated duodenal bicarbonate secretion. Am J Physiol 256:G833-G836, 1989
Nylander O, Hällgren A, Holm L: Duodenal mucosal alkaline secretion, permeability, and blood flow. Am J Physiol 265:G1029-G1038, 1993
Lenz HJ, Forquignon I, Drüge G, Greten H: Effects of neuropeptides on gastric acid and duodenal bicarbonate secretions in freely moving rats. Regul Pept 24:293–300, 1989
Mertz-Nielsen A, Hillingso J, Bukhave K, Rask-Madsen J: Omeprazole increases duodenal bicarbonate secretion in man. Gastroenterology 106:A-138, 1994 (abstract)
Guttu K, Rosok B, Gislason H, Fändriks L, Svanes K, Gronbech JE: Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat. Scand J Gastroenterol 26:431–441, 1991
Konturek SJ, Cieszkowski M, Kwiecien N, Konturek J, Tasler J, Bilski J: Effects of omeprazole, a substituted benzimidazole, on gastrointestinal secretions, serum gastrin, and gastric mucosal blood flow in dogs. Gastroenterology 86:71–77, 1984
Flemström G, Mattsson H: Effects of omeprazole on gastric and duodenal bicarbonate secretion. Scand J Gastroenterol 21(suppl 118):65–67, 1986
Fändriks L, Jönson C: Effects of acute administration of omeprazole or ranitidine on basal and vagally stimulated gastric acid secretion and alkalinization of the duodenum in anaesthetized cats. Acta Physiol Scand 138:181–186, 1990
Knutson L, Flemström G, Gustavsson S, Jedstedt G, Lönnerholm G: HCO3 secretion in rat duodenum after treatment with omeprazole and ranitidine. Scand J Gastroenterol 22:87–90, 1987
Dayton MT, Schlegel J: Cimetidine-induced bicarbonate production in canine gastric pouches. J Surg Res 32:464–470, 1982
Smith JL, Gamal MA, Chremos AN, Graham DY: Famotidine, a new H2-receptor antagonist: Effect on parietal, nonparietal, and pepsin secretion in man. Dig Dis Sci 30:308–312, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Inada, I., Satoh, H. Capsaicin-sensitive sensory neurons are involved in bicarbonate secretion induced by lansoprazole, a proton pump inhibitor, in rats. Digest Dis Sci 41, 785–790 (1996). https://doi.org/10.1007/BF02213135
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02213135