Abstract
1. The effects of secretin, glucagon, cholecystokinin-pancreozymin (CCK-PZ), gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP), somatostatin, neurotensin and enkephalin on basal, pentagastrin- and histamine-stimulated gastric acid secretion were investigated in the conscious fistula rat. 2. Glucagon and GIP were ineffective inhibitors of basal and pentagastrin-stimulated secretion. CCK-PZ stimulated acid secretion at a low dose level but at higher doses it inhibited both pentagastrin- and histamine-induced secretions. VIP was ineffective at low doses and at high doses its action was complicated by reflux of stimulated pancreatic and intestinal secretions into the stomach. Met-enkephalin inhibited histamine- but not pentagastrin-stimulated secretion. Neurotensin inhibited the response to pentagastrin but had no effect on histamine-stimulated secretion. Secretin and somatostatin were potent inhibitors of basal and pentagastrin-stimulated acid secretion with little or no effect on the response to histamine. 3. At doses completely inhibitory to pentagastrin-stimulated secretion secretin and somatostatin did not block the mobilization of gastric mucosal histamine by pentagastrin, although somatostatin caused partial competitive inhibition at lower doses of pentagastrin. Thus secretin and somatostatin inhibited pentagastrin-induced secretion neither by blocking gastric mucosal histamine mobilization nor by abolishing the direct action of histamine on the parietal cell -- findings which are inconsistent with the proposed role of histamine as the mediator of the action of gastrin on the parietal cell.