AJP - Gastrointestinal and Liver Physiology, Vol 243, Issue 6 505-G510, Copyright © 1982 by American Physiological Society
Inhibition of acid secretion in isolated gastric glands by substituted benzimidazoles
E. Fellenius, B. Elander, B. Wallmark, H. F. Helander and T. Berglindh
A new class of gastric acid inhibitors, substituted benzimidazoles (H 83/69
and H 149/94), have been tested in an isolated rabbit gastric gland
preparation. Acid formation in the glands was stimulated by histamine,
dibutyryl cAMP (DBcAMP), and high extracellular K+ concentrations, and the
glandular secretory response was measured by changes in oxygen consumption
and in accumulation of the weak base [14C]aminopyrine (AP). The substituted
benzimidazoles inhibited AP accumulation induced by all stimulants in a
dose-dependent noncompetitive manner. In contrast, cimetidine only
inhibited histamine-induced AP accumulation. Basal AP accumulation, not
affected by cimetidine, was also inhibited by the substituted
benzimidazoles, as was the increase in glandular oxygen consumption
produced by the addition of histamine and DBcAMP. Basal oxygen consumption
was inhibited by about 15%. The substituted benzimidazoles, like AP, are
weak bases and were also found to accumulate in the glands.
Semiquantitative morphological studies of glands stimulated by histamine
plus theophylline did not show any change in the enlarged secretory surface
area after stimulation in the presence of inhibitory concentrations of H
149/94 (10(-4) M). The results suggest that substituted benzimidazoles have
a mechanism of action different from that of H2-receptor antagonists and
indicate a very distal site of action in the events leading to acid
formation.
