Enprostil reduces the increase of gastric corpus mucosal mass induced by the hydrogen-potassium-stimulated adenosine triphosphatase inhibitor BY 831-78 in the rat.
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 micrograms/kg b.i.d.), BY 831-78 (15 mumol/kg once daily), the combination of enprostil and BY 831-78, ranitidine (300 mumol/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 less than 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 less than 0.01), whereas BY 831-78 prevented the enprostil-induced increase of antral mucosal volume (42 +/- 3 vs. 56 +/- 3 mm3, p less than 0.01). These results demonstrate that some of the trophic effects induced by a hydrogen-potassium-stimulated adenosine triphosphatase inhibitor are not exclusively governed by gastrin.
Inauen
W
W
Gastrointestinal Unit, University Hospital, Inselspital, Bern, Switzerland.
Rohner
C
C
Koelz
H R
HR
Herdmann
J
J
Schürer-Maly
C C
CC
Varga
L
L
Halter
F
F
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles; D016620:Enprostil; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D005755:Gastrins / Q000097:blood; D017506:H(+)-K(+)-Exchanging ATPase; D006863:Hydrogen-Ion Concentration; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000097:blood
D001562:Benzimidazoles; D005755:Gastrins; D011459:Prostaglandins E, Synthetic; C061000:BY 831-78; D013004:Somatostatin; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D016620:Enprostil