Roles of prostaglandins, nitric oxide, and the capsaicin-sensitive sensory nerve in the gastroprotection by the locally acting antiulcer drug ecabet sodium

• Published in: Japanese Journal of Pharmacology Vol. 67; no. suppl.1; p. 202
• Main Authors: Kinoshila, Mine, Saito, Nobuko
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1995
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)46772-3

A study was undertaken to determine the roles of prostaglandins (PGs), nitric oxide (NO) and the capsaicinsensitive sensory nerve (CPSN) in the gastroprotective effect of ecabet sodium (ecabet), a new antiulcer drug known to increase gastric mucosal prostaglandin E_2 (PGE_2 ) formation Either pretreatment with indomethacin (5 mg/kg, s.c.) or functional ablation of CPSN by systemic administration of a high dose of capsaicin (125 mg/kg, s.c.) partly reduced the gastroprotective activity of ecabet (25 and 100 mg/kg, p.o.) against ethanol-induced lesions. However, the former treatment completely abolished the ecabet-induced increase in PGE_2 formation, but the latter did not affect the stimulatory effect of ecabet on PGE_2 formation. Pretreatment with N^G -monomethyl-L-arginine (L-NMMA; 25-100 mg/kg, i.v.), an inhibitor of NO synthase, dose-dependently reduced the gastroprotective effects of both ecabet (25 and 100 mg/kg, p.o.) and capsaicin (0.5 mg/kg, p.o.); L-NMMA (100 mg/kg) reversed the gastroprotective effect of ecabet partly and that of capsaicin completely. The effect of L-NMMA against the protection of ecabet and capsaicin was abolished by pretreatment with L-arginine (100 mg/kg, i.v.), but not with D-arginine (100 mg/kg, i.v.). Although the gastroprotective activity of ecabet (25 mg/kg, p.o.) was fully reversed by pretreatment with indomethacin in combination with L-NMMA or CPSN-ablation, a combination of L-NMMA and CPSN-ablation did not give any additional suppressive effect on the effect by either treatment atone. These findings indicate that the gastroprotection by ecabet is cooperatively mediated by endogenous PGs and CPSN-related endogenous NO.