BACKGROUND The antiulcer drug ecabet 2Na (12-sulfodehydroabietic acid disodium salt) exhibits a gastroprotective activity, mainly through a local action, involving endogenous prostaglandins (PGs) and nitric oxide (NO). In the present study, we examined the effect of ecabet on the epithelial restitution of the bullfrog gastric mucosa in vitro following injury by hypertonic NaCl. METHODS Bullfrog fundic mucosa was mounted in an Ussing chamber. The 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 added to the luminal solution for 10 min before or after NaCl, while 16,16-dimethyl PGE(2) (dmPGE(2): 1x 10(-6) M) or NOR-3 (a NO donor: 1 x 10(-4) M) was added to the nutrient solution 10 min before NaCl. RESULTS Mucosal application of 1.25 M NaCl caused an immediate reduction of PD and R, followed by a gradual normalization, reaching about 70% of the pre-exposure levels within 4 h. Ecabet, added before NaCl, significantly expedited the recovery of 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 by serosal application of either dmPGE(2) or NOR-3. The mucosal exposure to ecabet significantly increased the luminal release of PGE(2) and NO metabolites, the effects being attenuated by indomethacin and L-NAME, respectively. The mucous secretion was increased by ecabet as well as dmPGE(2) and NOR-3, and the effect of ecabet was significantly suppressed by both indomethacin and L-NAME. The inhibitory effects of L-NAME on the ecabet action were all significantly antagonized by concurrent addition of L-arginine. CONCLUSION These results suggest that ecabet significantly expedited the restitution following gastric surface cell injury, and this action is mediated by endogenous NO as well as PGs and may be functionally associated with an increase of mucous secretion.