Inhibition of gastric acid secretion by omeprazole in the dog and rat

Larsson, Håkan; Carlsson, Enar; Junggren, Ulf; Olbe, L; Sjöstrand, Sven Erik; Skånberg, Inger; Sundell, Gunhild

doi:10.1016/0016-5085(83)90442-0

Cited by 240 publications

(69 citation statements)

References 7 publications

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“…c : served that it was possible to mimic endogenous gastrin levels resulting from achlorhydria [23]. However, omeprazole at a dose of 20 µmol/kg per day is known to abolish acid secretion in the rat [20]. In the present study, infusion through venous catheterisation was preferred to gastric intubation because mechanical irritation of the oesophagus by the tube could have influenced local cell renewal.…”

Section: Discussionmentioning

confidence: 93%

Gastrin stimulates epithelial cell proliferation in the oesophagus of rats

Nieuwenhove¹,

Backer

Chen

et al. 1998

Virchows Archiv

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Gastrin can induce mitotic stimulation in the oxyntic mucosa of the stomach, sometimes leading to abnormal growth. We examined whether gastrin was able to influence cell proliferation in the oesophageal epithelium. Rats were treated with gastrin, omeprazole or saline for 3 days, or were subjected to fundectomy or sham operation. Bromodeoxyuridine labelling (LI) and mitotic (MI) indices were counted in the proliferative zone of the squamous epithelium. Infusion of exogenous gastrin, treatment with omeprazole or fundectomy raised the LI and the MI values in the oesophageal epithelium, indicating that gastrin stimulates cell proliferation in the oesophageal mucosa in the rat.

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Section: Discussionmentioning

confidence: 93%

Gastrin stimulates epithelial cell proliferation in the oesophagus of rats

Nieuwenhove¹,

Backer

Chen

et al. 1998

Virchows Archiv

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“…In contrast, the anti-ulcerogenic potential of rohitukine under in vivo experiments was found as effective as omeprazole. The possible explanation for these observations might be the fact that the antisecretory functions of omeprazole is not dependent on secretagogues of gastric acid (Larsson et al 1983) while rohitukine may exert its Fig. 6 Effect of rohitukine (dose dependent) on intracellular Ca 2+ level in comparison to cholecystokinin receptor antagonist Benzotript.…”

Section: Discussionmentioning

confidence: 96%

Gastroprotective effect of anti-cancer compound rohitukine: possible role of gastrin antagonism and H+ K+-ATPase inhibition

Singh

Shrivastva

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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The present study was designed to evaluate the anti-ulcerogenic properties of an alkaloid chromane, rohitukine from Dysoxylum binectariferum. Anti-ulcer potential of rohitukine was assessed in cold restrained, pyloric ligated and ethanol induced ulcers in rats. In addition, rohitukine was tested in vitro for H(+) K(+)-ATPase inhibitory activity in gastric microsomes. Moreover, we studied the role of rohitukine on the cytosolic concentration of Ca(2+) in parietal cell-enriched cell suspension in order to ascertain its mechanism of action. Cytoprotective activity was evaluated through PGE(2) level. Rohitukine significantly attenuated the ulcers in cold restraint ulcer (CRU) model in a dose-related manner. Moreover, it significantly lowered the free acidity and pepsin activity in pyloric ligated rats while improved the depleted level of mucin. Furthermore, rohitukine significantly reversed the cold restrained-induced increase in gastrin level. Our in vitro study revealed that rohitukine moderately inhibited the microsomal H(+) K(+)-ATPase activity with respect to positive control omeprazole. Furthermore, rohitukine potently antagonized the gastrin-elicited increase in cytosolic Ca(2+) level in parietal cell-enriched suspension. In ethanol-induced gastric lesions in rats, rohitukine significantly inhibited the formation of erosions and increased PGE(2) content showing more potency than reference drug sucralfate. Our results thus suggest that rohitukine possess significant anti-ulcer and anti-gastrinic activity in rats. It is likely that gastro-protective influences of rohitukine are dependent partly on its acid-lowering potential and partly on cytoprotective property. The acid-reducing effect of rohitukine might be attributed to its lowering effect on gastrin production and/or antagonism of gastrin-evoked functional responses of parietal cells. Thus, rohitukine represent a useful agent in the treatment of peptic ulcer disease.

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“…OPZ, LPZ and PPZ , which have a benzimidazole structure, are transformed to active form (cationic sulfenamide) in the parietal cells under acidic condition and inhibit gastric acid secretion by forming a disulfide bond with the sulfhydryl groups of H+,K+-ATPase (8)(9)(10)(11)(12). It is well known that the inhibitory effect of the PPIs on acid secretion persists for a long time, in contrast with their rapid elimination from the plasma (13)(14)(15)(16). It has also been reported that this effect is closely related to area under the plasma concentration-time curve (AVC) after administration of OPZ (17,18).…”

Section: Introductionmentioning

confidence: 99%

Comparative pharmacokinetic/pharmacodynamic analysis of proton pump inhibitors omeprazole, lansoprazole and pantoprazole, in humans

Katashima

Yamamoto

Tokuma

et al. 1998

European Journal of Drug Metabolism and Pharmacokinetics

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The relationship between plasma concentrations and inhibitory effects on gastric acid secretion by proton pump inhibitors (PPIs) omeprazole (OPZ), lansoprazole (LPZ) and pantoprazole (PPZ), was analyzed using a pharmacokinetic/pharmacodynamic (PK/PD) model in humans. The estimated values of apparent reaction rate constant of PPI and H+,K+-ATPase (K) were 1.34 +/- 0.17 (microM(-1) x h(-1)), 0.339 +/- 0.002 and 0.134 +/- 0.006 for OPZ, LPZ and PPZ, respectively. The estimated values of apparent turn-over rate constant of H+,K+-ATPase (k) were 0.0252 +/- 0.0019 (h(-1)), 0.0537 +/- 0.0006 and 0.0151 +/- 0.0002 for OPZ, LPZ and PPZ, respectively. The apparent dissociation constants of the H+,K+-ATPase-PPI complex (k/K x fp) corrected with plasma free fraction (fp) were about 1 nM for OPZ and LPZ and 2.3 nM for PPZ. Therefore, the potency of the inhibitory effect of PPZ on acid secretion may be slightly weaker than that of OPZ or LPZ. The apparent half lives (ln2/k) of the inhibitory effect on acid secretion were 12.9 h for LPZ, < 27.5 h for OPZ, and < 45.9 h for PPZ, the recovery rate of the inhibitory effect of PPZ on acid secretion was slowest among these PPIs. In conclusion, the relationship between plasma concentrations and inhibitory effects of PPIs on gastric acid secretion could be analyzed by the PK/PD model.

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Inhibition of gastric acid secretion by omeprazole in the dog and rat

Cited by 240 publications

References 7 publications

Gastrin stimulates epithelial cell proliferation in the oesophagus of rats

Gastrin stimulates epithelial cell proliferation in the oesophagus of rats

Gastroprotective effect of anti-cancer compound rohitukine: possible role of gastrin antagonism and H+ K+-ATPase inhibition

Comparative pharmacokinetic/pharmacodynamic analysis of proton pump inhibitors omeprazole, lansoprazole and pantoprazole, in humans

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