AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 5 723-G731, Copyright © 1988 by American Physiological Society

ARTICLES

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

R. C. Thirlby, M. H. Stevens, A. J. Blair, F. Petty, I. L. Crawford, I. L. Taylor, J. H. Walsh and M. Feldman
Department of Surgery, Veterans Administration Medical Center, Dallas 75216.

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.