Role of Nitric Oxide and Prostaglandin in the Protective Effect of Pibutidine (cas 103922-33-4) Hydrochloride, a Novel Histamine H2-Receptor Antagonist, on the Gastric Mucosal Lesions in Rats

Add time:07/23/2019    Source:sciencedirect.com

1.The role of endogenous nitric oxide (NO) and prostaglandins (PGs) in the gastric mucosal protective action of Pibutidine (cas 103922-33-4) 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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