HISTAMINE H-2-RECEPTOR ANTAGONISTS STIMULATE PROLIFERATION BUT NOT MIGRATION OF HUMAN GASTRIC-MUCOSAL CELLS IN-VITRO

Gastric mucosal cell migration and proliferation are crucial events in the repair of gastric mucosal erosions. This study was designed to te st the hypothesis that the H-2 blockers roxatidine and ranitidine migh t stimulate migration and proliferation of gastric mucous cells derive d from a human well-differentiated gastric adenocarcinoma cell line (M KN 28 cells) in vitro, in conditions independent of systemic factors a nd of acid inhibition. Confluent monolayers of MKN 28 cells were wound ed with a razor blade and were then incubated with roxatidine or ranit idine. The number of cells migrating to the damaged area was determine d 24 hr later, Cell proliferation was assessed by means of [H-3]thymid ine uptake and cell counts after incubation with roxatidine or ranitid ine. Neither H-2 antagonist significantly stimulated cell migration, O n the other hand, cell proliferation was dose-dependently and signific antly enhanced by incubation with roxatidine and ranitidine, Exogenous administration of TGF-alpha significantly stimulated MKN 28 cell divi sion, However, incubation with roxatidine or ranitidine did not increa se the steady-state mRNA expression of TGF-alpha or EGFR as assessed b y northern blot analysis, Based on these in vitro findings, we postula te that the ulcer healing effect of these H-2 antagonists in vivo migh t be due in part to stimulation of gastric mucosal cell proliferation.