Involvement of gamma-aminobutyric acid in the stimulatory effect of metoclopramide on gastrointestinal motility.
The involvement of gamma-aminobutyric acid (GABA) in the mechanism of action of metoclopramide (MCP) on gastrointestinal (GI) tract was investigated employing guinea-pig myenteric plexus longitudinal muscle preparations. MCP induced a concentration dependent enhancement of electrically induced twitch responses of the myenteric plexus and this effect was further intensified by arecaidine and L-2, 4-diaminobutyric acid (L-DABA; GABA uptake inhibitors) and ethylenediamine (EDA; GABA releasing agent). The facilitatory effect of MCP was reduced by 3-mercaptopropionic acid (3-MPA; GABA synthesis and release inhibitor) and after GABA desensitization but remained unchanged after bicuculline methiodide, a specific GABA receptor antagonist. The MCP induced contraction of the unstimulated preparation was also reduced after GABA desensitization and EDA without affecting responses to exogenous acetylcholine (ACh). The study indicates that GABA plays a role in the facilitatory effect of MCP on both stimulated and unstimulated preparations of guinea pig myenteric plexus.