Effect of a histamine H-1 receptor antagonist on gastric endocrine cell proliferation induced by chronic acid suppression in rats

The effect of histamine on gastrin cells and enterochromaffin-like cells ha s not yet been clarified. We investigated the influence of pyrilamine (a hi stamine H-1 receptor antagonist) on serum gastrin level, gastrin cells, and enterochromaffin-like cells in rats with or without 4 weeks of famotidine treatment. The rats were divided into six groups: a control group, two pyri lamine groups (2 mg/kg, or 20 mg/kg, p.o.), a famotidine group (20 mg/kg tw ice/daily i.m.), and two pyrilamine + famotidine groups. The serum gastrin concentration was determined, and gastrin cells and enterochromaffin-like c ells were identified by the labeled streptavidin biotin complex method and counted. Hypergastrinemia, gastrin cell hyperplasia, and enterochromaffin-l ike cell hyperplasia were found after 4 weeks of famotidine treatment. Four weeks of treatment with pyrilamine alone did not affect the gastrin level, gastrin cells, or enterochromaffin-like cells in the rat stomach. When com bined with famotidine, pyrilamine enhanced famotidine-induced hypergastrine mia, but it did not affect gastrin cell hyperplasia, and it significantly i nhibited enterochromaffin-like cell hyperplasia. These results suggest that gastrin secretion and enterochromaffin-like cell proliferation may be regu lated by histamine via the H-1 receptor during acid suppression.