Effect of GABA on basal and vagally mediated gastric acid secretion and hormone release in dogs

Abstract

To stimulate peripheral gamma-aminobutyric acid (GABA) receptors, GABA, which does not cross the blood-brain barrier, was administered to dogs with vagally innervated gastric fistulas at intravenous doses of 0, 0.66, 2, 6, 18, and 54 micrograms.kg-1.min-1. Mean gastric acid output increased from zero basally to 3.0 +/- 1.4 mmol/h during infusion of 54 micrograms.kg-1.min-1 GABA. Plasma somatostatin-like immunoreactivity decreased significantly below basal levels during infusion of 54 micrograms.kg-1.min-1 GABA (P less than 0.05). To stimulate central nervous system GABA receptors as well as peripheral GABA receptors, progabide, a GABA-receptor agonist, which readily crosses the blood-brain barrier, was injected intravenously. Mean acid output was 3.5 +/- 1.3 mmol/h after 20 mg/kg progabide and 0.6 +/- 0.5 mmol/h after its vehicle (P less than 0.05). Basal serum gastrin concentration increased significantly after progabide injection. Acid output during insulin-induced hypoglycemia was inhibited 59% by 30 mg/kg intravenous progabide. Progabide infusion also diminished or abolished circulating gastrin, somatostatin, and pancreatic polypeptide responses during insulin-induced hypoglycemia (P less than 0.05). Further studies were performed in dogs with a gastric fistula and a vagally denervated Heidenhain pouch to confirm that GABA-receptor stimulation affects acid secretion via peripheral pathways. Intravenous injection of baclofen (0.5 mg/kg), a GABAB-receptor agonist, increased acid secretion significantly from the gastric fistula and the Heidenhain pouch. These studies suggest that GABA may play a role in regulating gastric acid secretion and gastrointestinal and pancreatic endocrine function by both central and peripheral mechanisms.