Effects of NC-1300-0-3 on Gastric Mucus Secretion and Prostaglandin Release in Rats

Matsukura, Hitoshi; Masuda, Makoto; Uchida, Aoi; Kamishiro, Toshiro

doi:10.1254/jjp.65.319

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…Our results support the previous ones of Matsukura et al [4,5] and Ishihara et al [6] that leminoprazole induces an accumu- Fig. 7.…”

Section: Discussionsupporting

confidence: 93%

“…The protective effect of leminprazole is considered to be through its antisecretory effect, mucus synthesis-promoting effect, and direct cytoprotec- Takahashi/Okabe tive effect on gastric epithelial cells [1,[3][4][5][6][7][8][9][10]. It was reported that accumulation of mucus glycoproteins in the gastric mucosa is observed after the oral administration of leminoprazole to rats [4][5][6]. In vitro studies also revealed that leminoprazole enhances mucus synthesis by rat gastric strips and rabbit gastric mucosal cells [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

Takahashi

Okabe²

1998

Pharmacology

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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 N^G-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.

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“…Our results support the previous ones of Matsukura et al [4,5] and Ishihara et al [6] that leminoprazole induces an accumu- Fig. 7.…”

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

Takahashi

Okabe²

1998

Pharmacology

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“…Therefore, since the present gastroprotective effects of pantoprazole were prevented by both NEM and indomethacin, it is likely that this drug exerts a positive influence on sulfhydryl compounds which, in turn, lead to an increased production of mucosal prostaglandins and an enhancement of the gastric mucus barrier. In support of this hypothesis, it was previously found that other benzimidazole derivatives promoted the release of prostaglandins into the gastric lumen of rats [36] and exerted gastroprotective effects which were reversed by NEM [45]. Furthermore, omeprazole increased both mucosal blood flow and gastroduodenal bicarbonate secretion [46][47][48], two effects which might result from an enhancement of endogenous prostaglandin release [13, 491. The comparison between pantoprazole and omeprazole performed in the present study showed that the former drug is more active in terms of both acid inhibition and gastroprotective effects.…”

Section: Role Of Endogenous Factors In the Protective Action Of Pantomentioning

confidence: 81%

Gastroprotective effects of pantoprazole against experimental mucosal damage

Blandizzi

Natale

Gherardi

et al. 2000

Fundamemntal Clinical Pharma

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The present study investigated the gastroprotective effects of the proton pump inhibitor pantoprazole on gastric mucosal damage induced by ethanol-HCl in rats. Omeprazole was used as reference drug. The morphometric analysis of gastric histological sections revealed that pantoprazole and omeprazole dose-dependently prevented the necrotic mucosal injury evoked by ethanol-HCl (ED50 = 14.1 and 21.6 micromol/kg, respectively). These effects were associated with a marked increment of Alcian blue recovery from gastric bound mucus (ED50 = 18.8 and 29.3 micromol/kg, respectively). In addition, both pantoprazole and omeprazole inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 1.5 and 3.3 micromol/kg, respectively). Further experiments indicated that the protective effects of pantoprazole were not modified by L-365,260 (a gastrin receptor antagonist), suramin (a drug able to interfere with endogenous growth factors), N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin (an inhibitor of prostaglandin synthesis) and fully prevented by N-ethylmaleimide (a potent blocker of sulfhydryl compounds). The present data provide histomorphometric evidence that: 1) pantoprazole is endowed with gastroprotective properties and is more active than omeprazole in preventing the necrotic mucosal damage induced by ethanol-HCl; 2) according to the rank order of ED50 values, the protective effects of both drugs appear to depend mainly on the enhancement of the gastric mucosal barrier rather than on the inhibition of acid secretion; 3) an increased production of prostaglandins, as well as an increased availability of sulfhydryl radicals at the level of the gastric mucosa may account for the gastroprotective effects of pantoprazole.

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“…The involve ment of prostaglandins in antiulce r action of proton pump inhibitors is controve rsial. Timoprazole and ome prazole stimulate prostaglandin production in vivo (23,34) . Howe ve r, pre treatme nt with indomethacin doe s not interfe re with the prote ctive e ffe cts of omeprazole (3), and this proton pump inhibitor doe s not stimulate prostaglandin synthe sis in culture d gastric mucosal cells (35,36) .…”

Section: Discussionmentioning

confidence: 99%

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Blandizzi

Natale²,

Gherardi³

et al. 1999

Digestive Diseases and Sciences

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The protective effects of the proton pump inhibitor lansoprazole on gastric mucosal damage induced by ethanol-HCl or hemorrhagic shock were investigated in the present study. The morphometric analysis of gastric histological sections revealed that lansoprazole dose-dependently reduced mucosal injury evoked by ethanol-HCl (ED50 = 24.3 micromol/kg) or hemorrhagic shock (ED50 = 38.9 micromol/kg), these effects being associated with marked increments of Alcian blue recovery from gastric bound mucus (ED50 = 31.4 micromol/kg and 27.6 micromol/kg, respectively). In addition, lansoprazole inhibited gastric acid secretion from pylorus-ligated rats (ED50 = 9.8 micromol/kg). Further experiments, performed on rats with ethanol-HCl-induced gastric injury, indicated that the protective effects of lansoprazole were not modified by L-365,260, suramin, N(G)-nitro-L-arginine, or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin and fully prevented by N-ethyl-maleimide. In addition, lansoprazole did not modify somatostatin concentrations in gastric mucosa. The present results provide evidence that lansoprazole prevents the necrotic damage of gastric mucosa induced by ethanol-HCl or hemorrhagic shock. According to the rank order of ED50 values, these effects appear to depend mainly on the enhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It is also proposed that an increased production of prostaglandins, as well as an increased availability of sulfhydryl compounds at level of gastric mucosa may account for the gastroprotective effects of lansoprazole.

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Effects of NC-1300-0-3 on Gastric Mucus Secretion and Prostaglandin Release in Rats

Cited by 6 publications

References 18 publications

Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

Gastroprotective effects of pantoprazole against experimental mucosal damage

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