Enprostil reduces the increase of gastric corpus mucosal mass induced by the hydrogen-potassium-stimulated adenosine triphosphatase inhibitor BY 831-78 in the rat

Abstract

We studied whether enprostil, a synthetic prostaglandin E2 derivative, might inhibit gastrin release and the trophic effects on gastric oxyntic mucosa induced by prolonged treatment with an inhibitor of hydrogen-potassium-stimulated adenosine triphosphatase, the substituted benzimidazole BY 831-78. Rats were treated intragastrically with enprostil (1 or 15 μg/kg b.i.d.), BY 831-78 (15 μmol/kg once daily), the combination of enprostil and BY 831-78, ranitidine (300 μmol/kg b.i.d.), and placebo. Plasma gastrin and somatostatin levels and gastric acid secretion were measured during a 1-day treatment in animals fitted with chronic gastric fistulas and repeatedly during 9 wk of treatment in intact rats. Despite inhibiting acid secretion, enprostil did not increase plasma gastrin. When combined with BY 831-78, enprostil transiently reduced the BY 831-78-induced increase of integrated plasma gastrin (1375 ± 206 vs. 2137 ± 256 pmol/L · 12 h, p < 0.05) in fasted rats with fistulas, but failed to prevent the marked hypergastrinemia following 9 wk of treatment with BY 831-78 (717 ± 80 vs. 731 ± 56 pmol/L) in intact rats. However, enprostil reduced the BY 831-78-induced increase of oxyntic mucosal volume (458 ± 31 vs. 567 ± 33 mm3, p < 0.01), whereas BY 831-78 prevented the enprostil-induced increase of antrat mucosal volume (42 ± 3 vs. 56 ± 3 mm3, p < 0.01). These results demonstrate that some of the trophic effects induced by a hydrogen-potassiumstimulated adenosine triphosphatase inhibitor are not exclusively governed by gastrin.