Effect of GABA on basal and vagally mediated gastric acid secretion and hormone release in dogs.
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.
Thirlby
R C
RC
Department of Surgery, Veterans Administration Medical Center, Dallas 75216.
Stevens
M H
MH
Blair
A J
AJ
Petty
F
F
Crawford
I L
IL
Taylor
I L
IL
Walsh
J H
JH
Feldman
M
M
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D005755:Gastrins / Q000097:blood; D005768:Gastrointestinal Hormones / Q000097:blood*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D011963:Receptors, GABA-A / Q000378:metabolism; D014630:Vagus Nerve / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D001786:Blood Glucose; D005755:Gastrins; D005768:Gastrointestinal Hormones; D007328:Insulin; D011963:Receptors, GABA-A; C017985:progabide; D005680:gamma-Aminobutyric Acid; D001418:Baclofen