The role of substance P in the control of gastric acid secretion

Experiments were performed to determine whether substance P plays a physiologic role as an enterogastrone. Basal substance P levels averaged 6.4 +/- 0.2 pg/ml in dogs prepared with gastric and duodenal fistulas. Infusion of substance P at 5 ng/kg/min increased circulating hormone concentrations by more than 1 pg/ml and inhibited pentagastrin-stimulated (4 micrograms/kg/hr) gastric acid secretion by 44% (from 10.9 +/- 1.8 to 6.1 +/- 1.6 mEq/30 min); a similar dose of substance P (7 ng/kg/min) did not alter gastrin levels from the basal level of 19.8 +/- 1.2 fmol/ml. Duodenal acidification (with 0.1N HCl at 5 ml/min for 10 minutes) similarly inhibited pentagastrin-stimulated gastric fistula output (from 8.2 +/- 0.9 to an average of 5.0 +/- 0.9 mEq/30 min for the 30 minutes after irrigation) but did not alter circulating substance P levels. Thus, although physiologic concentrations of substance P inhibit gastric fistula output, this peptide does not seem to be involved in the endogenous acid-mediated duodenal control of acid secretion.