Potentiation by baclofen of gastric acid secretion stimulated by secretagogues in vagotomized rats under anesthesia.
The effect of intravenous administration of baclofen, a GABA(B) receptor agonist, on gastric acid secretion from perfused stomach was studied in vagotomized rats anesthetized with urethane. Baclofen did not stimulate acid secretion by itself. In contrast, baclofen dose-dependently potentiated acid secretion induced by pentagastrin, bethanechol and direct vagal stimulation, but not by histamine. Baclofen-potentiated acid secretion induced by pentagastrin and bethanechol was not influenced by pretreatment with atropine or cimetidine, respectively. Baclofen-potentiated acid secretion evoked by direct vagal stimulation was prevented by pretreatment with proglumide which is a gastrin receptor antagonist. Baclofen-potentiated acid secretion evoked by bethanechol was partly prevented by bicuculline methiodide which is a GABA(A) receptor antagonist, but not by phaclofen which is a GABA(B) receptor antagonist, suggesting an involvement of peripheral GABA(A) receptors. Baclofen-potentiated acid secretion induced by direct vagal stimulation was not affected by the change of body temperature. These results suggest that baclofen stimulates acid secretion under certain conditions, and that two mechanisms are involved in this effect. The effects of baclofen on acid secretion may be mediated by increasing the release of histamine by pentagastrin, bethanechol and direct vagal stimulation. In addition, baclofen would also be effective if muscarinic agents were already occupying muscarinic acetylcholine receptors on parietal cells.
Lin W-C
Department of Pharmacology, China Medical College, Taiwan.
D000758:Anesthesia; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology*; D001626:Bethanechol Compounds / Q000494:pharmacology; D001831:Body Temperature / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014520:Urethane; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
D001626:Bethanechol Compounds; D018755:GABA Agonists; D018756:GABA Antagonists; C052329:phaclofen; D014520:Urethane; D010418:Pentagastrin; D001418:Baclofen