Effect of ecabet disodium, a novel locally-acting antiulcer drug. on epithelial restitution following injury by hypertonic NaCl in bullfrog stomach in vitro

Background: The antiulcer drug ecabet 2Na (12-sulfode-hydroabietic acid dis odium salt) exhibits a gastroprotective activity, mainly through a local ac tion, involving endogenous prostaglandins (PGs) and nitric oxide (NO). in t he present study, we examined the effect of ecabet on the epithelial restit ution of the bullfrog gastric mucosa in vitro following injury by hypertoni c NaCl. Methods: Bullfrog fundic mucosa was mounted in an Ussing chamber. T he tissue injury was induced by exposure of the mucosa to 1.25 M NaCl for 5 min, and transmucosal potential difference (PD) and electrical resistance (R) were measured during a 4-hour test period. Ecabet (3-30 mg/ml) was adde d to the luminal solution for 10 min before or after NaCl, while 16,16-dime thyl PGE(2) (dmPGE(2): 1 x 10(-6) M) or NOR-3 (a NO donor: 1 x 10(-4) M) wa s added to the nutrient solution 10 min before NaCl. Results: Mucosal appli cation of 1.25 M NaCl caused an immediate reduction of PD and R, followed b y a gradual normalization, reaching about 70% of the pre-exposure levels wi thin 4 h. Ecabet, added before NaCl, significantly expedited the recovery o f PD and R in a concentration dependent manner; this effect was mimicked by posttreatment with ecabet and significantly mitigated by prior addition of indomethacin (1 x 10(-5) M) or N-G-nitro-L-arginine methyl ester (L-NAME: 1 x 10(-3) M). The epithelial restitution was also significantly promoted b y serosal application of either dmPGE2 or NOR-3. The mucosal exposure to ec abet significantly increased the luminal release of PGE(2) and NO metabolit es, the effects being attenuated by indomethacin and L-NAME, respectively. The mucous secretion was increased by ecabet as well as dmPGE2 and NOR-3, a nd the effect of ecabet was significantly suppressed by both indomethacin a nd L-NAME. The inhibitory effects of L-NAME on the ecabet action were all s ignificantly antagonized by concurrent addition of L-arginine. Conclusion:T hese results suggest that ecabet significantly expedited the restitution fo llowing gastric surface cell injury, and this action is mediated by endogen ous NO as well as PGs and may be functionally associated with an increase o f mucous secretion. Copyright (C) 2000 S. Karger AG. Basel.