Stimulatory effect of muscimol on gastric acid secretion stimulated by secretagogues in vagotomized rats under anesthesia.

The effect of intravenous administration of muscimol, a GABAA receptor agonist, on gastric acid secretion from perfused stomach was studied in vagotomized rats anesthetized with urethane. Muscimol did not stimulate acid secretion by itself. In contrast, muscimol dose dependently potentiated acid secretion induced by pentagastrin, bethanechol and direct vagal stimulation, but not histamine. Muscimol-potentiated acid secretion induced by pentagastrin and bethanechol was not influenced by pretreatment with atropine or cimetidine, respectively. Muscimol-potentiated acid secretion evoked by direct vagal stimulation was prevented by pretreatment with proglumide, a gastrin receptor antagonist. Muscimol-potentiated acid secretion evoked by bethanechol was dose dependently prevented by bicuculline methiodide, suggesting an involvement of peripheral GABAA receptors. These results suggest that muscimol stimulates acid secretion under certain conditions, and that two mechanisms are involved in this effect. The effects of muscimol on acid secretion may be mediated by increasing the release of histamine by pentagastrin, bethanechol and direct vagal stimulation. In addition, muscimol would also be effective if muscarinic agents were already occupying muscarinic acetylcholine receptors on parietal cells.