GASTRIC-MUCOSAL EGF AND PDGF RECEPTOR EXPRESSION WITH ULCER HEALING BY EBROTIDINE

Objectives: Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) play important roles in the process of mucosal repair an d restitution, and their biological effects are mediated by receptors located on the target cell surfaces. The purpose of this study was to assess the effect of the antiulcer agent, ebrotidine, on the expressio n of EGF and PDGF receptors with chronic ulcer healing. Methods: Chron ic gastric ulcers were developed in the rat by acetic acid technique. The animal were divided into two groups and were treated twice daily f or 14 consecutive days, either with ebrotidine at 100 mg/kg, or placeb o. At different stages of treatment, the animals were sacrificed and u sed for the isolation and quantification of gastric mucosal EGF and PD GF receptors. Results: The binding assays revealed that ulcer healing was accompanied by an increase in mucosal expression of both types of receptors. A 1.7-1.8-fold increase in PDGF and EGF receptors occurred by the 4th day after the development of ulcer and reached a maximum of 3-fold increase by the 14th day, when the ulcer was essentially heale d. Treatment with ebrotidine caused accelerated ulcer healing (7 days) which was accompanied by a significant enhancement in receptor expres sion. Compared to the controls, a 1.5-fold increase in EGF and 1.7-fol d increase in PDGF receptor expression occurred by the 7th day of ebro tidine treatment, and a 1.4- to 1.5-fold increase was still observed a t the 14th day of treatment. Conclusions: The results suggest that ebr otidine is capable of enhancement of gastric mucosal proliferative act ivities associated with ulcer healing through the stimulation of EGF a nd PDGF receptor expression.