Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.

Abstract

Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK(2)/gastrin receptor antagonist) and ranitidine (histamine H(2) receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and N(G)-nitro L-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.

• Authors: S I Chandranath, S M A Bastaki, A D'Souza, A Adem, J Singh
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 349 Issue 1-2 Pg. 205-12 (Mar 2011) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 21116686 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 2-Pyridinylmethylsulfinylbenzimidazoles
• Indoles
• Phenethylamines
• Prostaglandin Antagonists
• Proton Pump Inhibitors
• Lansoprazole
• PD 136450
• Ranitidine
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester
• Indomethacin

Topics

• 2-Pyridinylmethylsulfinylbenzimidazoles (pharmacology)
• Administration, Oral
• Animals
• Indoles (pharmacology)
• Indomethacin (pharmacology)
• Injections, Subcutaneous
• Lansoprazole
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Phenethylamines (pharmacology)
• Prostaglandin Antagonists (pharmacology)
• Proton Pump Inhibitors
• Ranitidine (pharmacology)
• Rats
• Rats, Wistar
• Stomach Ulcer (drug therapy, etiology, pathology)
• Stress, Psychological (complications)