Central GABA-A receptors exert a tonic inhibitory control on gastric pepsinogen secretion in anaesthetized rats.
1. The purpose of the present study was to analyse the role played by central gamma-aminobutyric acid (GABA-A) receptors in the regulation of gastric basal pepsinogen secretion in anaesthetized rats. 2. The central, but not parenteral, administration of the GABA-A receptor antagonist bicuculline or SR-95531 caused a significant and dose-dependent increase in basal pepsinogen secretion without changes in acid output. The stimulant effect exerted by bicuculline was prevented by atropine or pirenzepine, but not by vagotomy. 3. The central, but not parenteral, administration of the GABA-A receptor agonist muscimol or THIP induced a significant and dose-dependent stimulation of both basal pepsinogen and acid secretion. The excitatory effect exerted by muscimol was prevented by atropine, pirenzepine, or pretreatment with omeprazole, but not by vagotomy. 4. These results suggest that central GABA-A receptors mediate a tonic inhibitory control on gastric pepsinogen secretion, while their phasic activation leads to an excitatory effect on acid output. However, the agonist-induced pepsigogue action appears to be generated peripherally as an indirect consequence of the increase in acid secretion. 5. It is also suggested that central GABA-A receptors affect the gastric secretory functions through non-vagal pathways that are sensitive to the blockade of peripheral cholinergic receptors.
Natale
G
G
Institute of Medical Pharmacology, School of Medicine and Dentistry, University of Pisa, Italy.
Blandizzi
C
C
Carignani
D
D
Colucci
R
R
Martinotti
E
E
Del Tacca
M
M
D000758:Anesthesia; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003864:Depression, Chemical; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010435:Pepsinogens / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D014628:Vagotomy
D018755:GABA Agonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010435:Pepsinogens; D011724:Pyridazines; D011963:Receptors, GABA-A; C049853:gabazine; D001640:Bicuculline