Peripheral 2-hydroxy-saclofen-sensitive GABA-B receptors mediate both vagal-dependent and vagal-independent acid secretory responses in rats.
1. The present study investigates the effects of peripherally administered baclofen on gastric acid secretion from the perfused stomach of anaesthetized rats. 2. Intravenous (i.v.) baclofen caused a marked dose-dependent increase in acid secretion which was antagonized by i.v. 2-hydroxy-saclofen, whereas intracerebroventricular (i.c.v.) 2-hydroxy-saclofen and i.c.v. or i.v. phaclofen and bicuculline were ineffective. In addition, 2-hydroxy-saclofen did not affect acid hypersecretion stimulated by histamine. 3. The secretagogue action of baclofen was fully prevented by cimetidine, but only partially attenuated by atropine, proglumide or bilateral cervical vagotomy. Moreover, the vagotomy-resistant excitatory effect of baclofen was abolished by 2-hydroxy-saclofen or cimetidine, but not by atropine or proglumide. 4. In vagotomized rats whose gastric secretion was maximally increased by electrical stimulation of the left vagus nerve, i.v. injection of baclofen further potentiated acid output, this action being prevented by cimetidine. 5. Taken together, the present results provide evidence that peripheral GABA-B receptors mediate the gastric hypersecretory effect of parenterally administered baclofen to anaesthetized rats, and suggest that both vagal cholinergic and extravagal pathways are involved in the stimulant effect.
Blandizzi
C
C
Institute of Medical Pharmacology, School of Medicine and Dentistry, University of Pisa, Italy.
Bernardini
M C
MC
Natale
G
G
Martinotti
E
E
Del Tacca
M
M
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D011963:Receptors, GABA-A; D001418:Baclofen; C057491:2-hydroxysaclofen