Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.
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.
Department of Pharmacology, Faculty of Medicine & Health Sciences, UAE University, Al Ain, United Arab Emirates.
S I
SI
Chandranath
S M A
SM
Bastaki
A
A
D'Souza
A
A
Adem
J
J
Singh
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007279:Injections, Subcutaneous; D064747:Lansoprazole; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010627:Phenethylamines / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D007211:Indoles; D010627:Phenethylamines; D011448:Prostaglandin Antagonists; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; C077645:PD 136450; D011899:Ranitidine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin