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Using antibodies to a complementary peptide of somatostatin, putative somatostatin binding proteins were characterized on canine parietal cells. A synthetic peptide (S-C1) was derived from the complementary mRNA sequence for somatostatin-14. Antiserum containing antibodies to S-C1 inhibited competitively 125I-Tyr11-somatostatin binding to canine oxyntic mucosal membranes. Canine parietal cell preparations were incubated with carbachol in the presence or absence of somatostatin and antisera to S-C1. Antibodies to S-C1 produced a decrease in carbachol-stimulated 14C-aminopyrine uptake comparable with that produced by 10(-6) M somatostatin. In immunocytochemical studies by light microscopy, antibodies to S-C1 produced positive staining of parietal cells throughout the oxyntic gland area. By electron microscopy using immunogold techniques, binding by antibodies to somatostatin C-1 was localized ultrastructurally to basolateral and intracellular membranes and to secretory canalicular membranes of parietal cells. These studies support the conclusion that antibodies to the somatostatin complementary peptide demonstrate properties similar to those of somatostatin in that they inhibit carbachol-stimulated aminopyrine uptake and 125I-somatostatin binding. Furthermore, these antibodies localize to specific regions on plasma membranes of parietal cells, which may represent somatostatin binding sites.

Previous studies have questioned the physiological role of gastric inhibitory peptide in inhibiting gastric acid secretion. The present study was designed to examine and compare peptone meal-stimulated gastric acid secretion in dogs after intravenous infusion of rabbit serum containing antibodies to gastric inhibitory peptide or normal rabbit serum (as control). Five dogs were prepared with gastric fistulas. Basal acid output was collected for 90 min through the gastric fistula. After 30 min of basal acid output collection, either rabbit serum containing antibodies to gastric inhibitory peptide or normal control rabbit serum (0.1 ml/kg) was infused intravenously over 1 min. After the basal acid output collection, a 10% peptone meal was infused into the stomach. Gastric acid output was measured by intragastric titration (pH 5.0) for 60 min. Peripheral venous plasma was collected for measurement of gastrin and gastric inhibitory peptide and for binding of endogenous plasma gastric inhibitory peptide by administered antibodies to gastric inhibitory peptide before and at 2, 5, 10, 15, 30, 60, 90, and 120 min after the meal. After intravenous administration of antibodies to gastric inhibitory peptide, 98% +/- 3% (SEM) of endogenous plasma gastric inhibitory peptide was bound by administered antibodies to gastric inhibitory peptide. No binding of endogenous plasma gastric inhibitory peptide was detected after infusion of normal rabbit serum. In dogs receiving intravenous antibodies to gastric inhibitory peptide, both peptone-stimulated gastric acid output and integrated gastrin release responses were increased when compared with dogs receiving normal rabbit serum. With infusion of antibodies to gastric inhibitory peptide, there was a high degree of correlation between the increase in gastric acid output and the increase in integrated gastrin response (r = 0.900, p less than 0.04) that followed the peptone meal. This study, using antibodies to bind endogenous gastric inhibitory peptide, demonstrates the capacity of circulating gastric inhibitory peptide to inhibit meal-stimulated gastric acid secretion. Furthermore, these results support the conclusion that this enterogastrone effect of gastric inhibitory peptide is due, at least in part, to inhibition of gastrin release.