Central GABAA excitatory and GABAB inhibitory receptors regulate gastric acid secretion in rats.
The present study investigates the effects of GABAA- and GABAB-receptor agonists and antagonists on gastric secretion after their i.c.v. administration to conscious pylorus-ligated rats and anaesthetized stomach lumen-perfused rats. Muscimol was without effect in pylorus-ligated rats, whereas baclofen produced a significant decrease in acid secretion, which was fully prevented by phaclofen. Under these conditions, a significant decrease in acid secretion was also obtained with bicuculline. In stomach lumen-perfused rats, muscimol caused a marked, dose-dependent increase in acid secretion, which was antagonized by bicuculline. Under the same conditions, baclofen induced a moderate, but significant, bicuculline-sensitive increase in acid secretion. Overall, our results suggest the presence of two central GABA pathways which mediate opposite effects: (a) a bicuculline-sensitive GABAA-receptor, the stimulation of which increases acid secretion under pharmacological depression of central vagal tone (anaesthetized rats); (b) a phaclofen-sensitive GABAB-receptor, the activation of which decreases vagally stimulated acid secretion (pylorus-ligated rats).
Del Tacca
M
M
Laboratory of Molecular Pharmacology, University of Pisa, Italy.
Blandizzi
C
C
Bernardini
M C
MC
D000758:Anesthesia; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002490:Central Nervous System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011708:Pylorus / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; C052329:phaclofen; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline