Peptide YY (PYY), a new peptide found primarily in mucosal endocrine cells of the terminal ileum and colon, inhibits pentagastrin-stimulated gastric acid secretion in several species, including man. Several studies indicate that PYY can affect autonomic neurotransmission, and we have recently shown that PYY can inhibit neurally stimulated release of insulin. The purpose of the present study was to examine the effect of PYY on gastric acid secretion stimulated by the autonomic nervous system. On separate days, 6 dogs that were prepared with chronic gastric cannulas were given 2-deoxy-D-glucose (2-DG; 90 mg/kg, i.v.) for 6 min, either alone, or in combination with PYY (100, 200, or 400 pmol.kg-1.h-1, i.v.) for 60 min. The effect of PYY, at 400 pmol.kg-1.h-1, on gastric acid secretion stimulated by either 2-DG or PG (1 micrograms.kg-1.h-1, i.v.) was studied after treatment with propranolol (0.5 mg/kg, i.v. bolus) or phentolamine 1 mg/kg, i.v. bolus). PYY reduced the 2-DG-stimulated secretion of gastric acid in a dose-dependent manner. PYY, given at 100 pmol.kg-1.h-1, reduced gastric acid output by 29 +/- 17%; PYY, at 200, by 41 +/- 7% (p < 0.05), and PYY, at 400, by 52 +/- 8% (p < 0.05). The inhibitory action of PYY on 2-DG-stimulated secretion of gastric acid persisted after treatment with phentolamine (69 +/- 14%; p < 0.05), but it was blocked by treatment with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)