Role of pepsin in the development of indomethacin-induced antral ulceration in the rat.
OBJECTIVE
To examine the effects of a pepsin inhibitor, pepstatin-A, a long acting H2-receptor blocker, loxtidine, exogenous pepsin and exogenous acid against indomethacin-induced antral ulceration in the rat.


RESULTS
Indomethacin (60 mg/kg s.c.) caused antral ulceration in fasted/re-fed rats over a period of 4 h. Ulceration was prevented in a dose-dependent manner by treatment with pepstatin-A (0.1-1 mg.kg hourly) or loxtidine (3 mg/kg) given orally. Acidified methylcellulose (1 mL hourly per os) enhanced damage and also prevented protection by loxtidine (3 mg/kg per os). The protection by pepstatin-A was not altered by treatment with acidified methylcellulose but was reversed by treatment with a 10-fold excess of pepsin.


CONCLUSIONS
These studies suggest that mucosal degradation by pepsin, rather than direct damage by luminal acid, was the major factor in the development of indomethacin-induced antral ulceration in the rat.
Gaw
A J
AJ
Peptic Ulceration Group, Glaxo Research and Development Ltd, Hertforshire, UK.
Williams
L V
LV
Spraggs
C F
CF
Jordan
C C
CC
D000818:Animals; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008747:Methylcellulose / Q000494:pharmacology; D010434:Pepsin A / Q000502:physiology*; D010436:Pepstatins / Q000494:pharmacology / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000503:physiopathology*; D011706:Pyloric Antrum / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D013997:Time Factors
D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D008747:Methylcellulose; D010434:Pepsin A; C031375:pepstatin; D007213:Indomethacin