Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new VI
P-like blain-gut peptide. Its effects on the motility and secretory fu
nctions of the gastrointestinal system have been shown in previous stu
dies. In this study we investigated the effect of intravenous PACAP on
gastric acid secretion in conscious pylorus-ligated rats and in gastr
ic fistula rats. PACAP showed significant inhibitory effects on pentag
astrin- and histamine-stimulated gastric acid secretion, but no effect
on basal or carbachol-stimulated secretion in pylorus-ligated rats. I
t did show dose-related inhibitory effects both on basal gastric acid
secretion and on secretion stimulated by pentagastrin, histamine, or c
arbachol in gastric fistula rats. PACAP did not alter serum gastrin le
vels. Inhibition of prostaglandin synthesis with indomethacin and immu
noneutralization of somatostatin with anti-somatostatin serum did not
prevent the inhibitory effect of PACAP on gastric acid secretion in py
lorus-ligated rats. We conclude that PACAP most likely has a direct ef
fect on parietal cells and that this effect may be mediated, at least
partially, by inhibition of the action of histamine on parietal cells.