ROLES OF PROSTAGLANDINS, NITRIC-OXIDE AND THE CAPSAICIN-SENSITIVE SENSORY NERVES IN GASTROPROTECTION PRODUCED BY ECABET SODIUM

We determined the mechanism of the gastroprotective effects of ecabet sodium (ecabet), a new antiulcer drug. Ecabet (12.5-100 mg/kg p.o.) do se-dependently protected gastric mucosa from ethanol-induced injuries in rats, as determined with the use of both macroscopic and microscopi c analyses. Both inhibition of prostaglandin (PG) formation by indomet hacin (5 mg/kg s.c.) and functional ablation of capsaicin-sensitive se nsory nerves (CPSN) by systemic administration of capsaicin (125 mg/kg s.c.) partly reduced the gastroprotective activity of ecabet (25 and 100 mg/kg p.o.). Ecabet increased rat gastric mucosal PGE, formation. The treatment with indomethacin but not capsaicin decreased the ecabet -induced increase in PGE(2) formation. inhibition of nitric oxide (NO) formation by N-G-monomethyl-L-arginine (L-NMMA; 100 mg/kg i.v.) partl y reversed the gastroprotective effect of ecabet and completely revers ed that of capsaicin at an oral dose of 0.5 mg/kg, respectively. The e ffect of L-NMMA was abolished by pretreatment with L-arginine (100 mg/ kg i.v.) but not with D-arginine (100 mg/kg i.v.). The gastroprotectiv e activity of ecabet (25 mg/kg p.o.) was fully reversed by pretreatmen t with indomethacin in combination with L-NMMA or CPSN ablation. On th e contrary, a combination of L-NMMA and CPSN atlation did not have add itional effect on the suppression by either treatment alone. These fin dings indicate that the gastroprotection by ecabet is cooperatively me diated by endogenous PGs and CPSN-related endogenous NO.