Previous studies have shown that pituitary adenylate cyclase-activating pep
tide (PACAP) stimulates enterochromaffin-like (ECL) cell histamine release,
but its role in the regulation of gastric acid secretion is disputed. This
work examines the effect of PACAP-38 on aminopyrine uptake in enriched rat
parietal cells and on histamine release and acid secretion in the isolated
vascularly perfused rat stomach and the role of PACAP in vagally (2-deoxyg
lucose) stimulated acid secretion in the awake rat. PACAP has no direct eff
ect on the isolated parietal cell as assessed by aminopyrine uptake. PACAP
induces a concentration-dependent histamine release and acid secretion in t
he isolated stomach, and its effect on histamine release is additive to gas
trin. The histamine H-2 antagonist ranitidine potently inhibits PACAP-stimu
lated acid secretion without affecting histamine release. Vagally stimulate
d acid secretion is partially inhibited by a PACAP antagonist. The results
from the present study strongly suggest that PACAP plays an important role
in the neurohumoral regulation of gastric acid secretion. Its effect seems
to be mediated by the release of ECL cell histamine.