1. The effect of antiulcer agents,
ebrotidine and
sucralfate, on the expression of gastric mucosal
proliferating cell nuclear antigen (
PCNA) and
cyclin-dependent kinase (p34Cdk2) during chronic
ulcer healing was examined. 2. Rats with experimentally induced
gastric ulcers were treated twice daily for 14 days with either
ebrotidine at 100 mg/kg,
sucralfate at 100 mg/kg or vehicle, and at different stages of treatment their stomachs were used for quantitization of gastric mucosal
PCNA and Cdk2 expression. 3. The assays revealed that the
ulcer healing was accompanied by a marked elevation in mucosal expression of
PCNA and Cdk2. The maximum increase in
PCNA (4.7-fold) occurred by the second day of healing, and the expression of Cdk2 reached a maximum increase (2.3-fold) by the fourth day. 4. Accelerated
ulcer healing with
ebrotidine (7 days) and
sucralfate (8 days) treatments was reflected in a significant enhancement of
PCNA and Cdk2 expression. By the second day of treatment,
ebrotidine evoked a 15-fold increase in
PCNA expression, and
sucralfate produced an 11.8-fold enhancement. The mucosal expression of Cdk2 attained a maximum of 4.3-fold increase over that of the controls by the sixth day of healing with
ebrotidine, and a fivefold increase in Cdk2 expression occurred by the fourth day of
ulcer treatment with
sucralfate. 5. The findings implicate
cell cycle regulatory proteins in the processes to leading to mucosal repair and suggest that the two drugs exert a similar effect on the expression of
proteins that control cell cycle progression.