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  • Title: Role of nitric oxide and prostaglandin in the protective effect of pibutidine hydrochloride, a novel histamine H2-receptor antagonist, on the gastric mucosal lesions in rats.
    Author: Kiuchi Y, Isobe Y, Kijima H, Saitoh T, Higuchi S.
    Journal: Gen Pharmacol; 1998 Aug; 31(2):271-5. PubMed ID: 9688471.
    Abstract:
    1. The role of endogenous nitric oxide (NO) and prostaglandins (PGs) in the gastric mucosal protective action of pibutidine hydrochloride (IT-066), a novel histamine H2-receptor antagonist, was investigated in a 0.15 N hydrochloride (HCl) + 60% ethanol (EtOH)-induced gastric lesion model. 2. The 0.15 N HCl + 60% EtOH-induced lesion formation was reduced significantly by IT-066 (3 mg/kg, PO), NOR3 (spontaneous NO releaser; 0.03-0.1 mg/kg, SC) or PGE2 (0.01 mg/kg, PO) but was not reduced by famotidine (1-10 mg/kg, PO). 3. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (3 mg/kg, IV), an inhibitor of NO synthase, inhibited the protective action of IT-066 (3 mg/kg, PO), and the inhibitory effect of L-NAME was reversed by L-arginine (300 mg/kg, IV). The protective effect of PGE2 (0.01 mg/kg, PO) was not affected by the pretreatment with L-NAME (3 mg/kg, IV). 4. Infusion of carboxy-PTIO (1 mg/kg/min), a direct NO scavenger, inhibited the protective effect of IT-066 (3 mg/kg, SC) or NOR3 (0.1 mg/kg, SC). Pretreatment with indomethacin (5 mg/kg, SC) markedly reduced the protective effect of IT-066 (3 mg/kg, PO) or NOR3 (0.1 mg/kg, SC). 5. These results suggest that endogenous NO and PGs may be implicated in the gastric mucosal protection induced by IT-066 and that the endogenous PGs may contribute to the protective effect of NO.
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