GASTRIC ECL-CELL HYPERPLASIA PRODUCES ENHANCED BASAL AND STIMULATED GASTRIC-ACID OUTPUT BUT NOT GASTRIC-EROSION FORMATION IN THE RAT

1. The purpose of this study was to examine the change in gastric acid output and gastric erosion formation produced by inducing gastric ent erochromaffin-like (ECL) cell hyperplasia in female rats. 2. Rats were treated with vehicle or ranitidine (1,200 mu mol/kg/day x 4 wks) admi nistered via SC Alzet minipumps. Experiments were performed 24 hours a fter removing the minipump, when the inhibitory effect of ranitidine o n gastric acid secretion had been lost. 3. Basal gastric acid secretio n was 7-fold higher in chronic ranitidine animals than in sham control . 4. Both total and net gastric acid secretions stimulated by carbacho l/pentagastrin infusion or histamine injection were significantly high er in chronic ranitidine animals than in controls. 5. By contrast, int racisternal injection of the chemical vagal stimulant RX77368 (100 ng) resulted in no net increase in acid output of the recovered ranitidin e pretreated group. 6. No significant changes in gastric erosions prod uced experimentally by cold exposure plus restraint or indomethacin pr etreatment were noted in recovered chronic ranitidine animals compared to sham controls. 7. These findings suggest that achlorhydria induced ECL cell hyperplasia augments both basal and stimulated gastric acid secretory function. The histamine results implicate an enhanced pariet al cell mass, upregulation of H-2 receptors, and/or second messenger e vents at the parietal cell as the mechanism for the enhanced gastric s ecretory response. Copyright (C) 1997 Elsevier Science Inc.