PROPOFOL'S BIPHASIC EFFECT ON GABAA-RECEPTOR-MEDIATED RESPONSE OF THE ISOLATED GUINEA PIG ILEUM

Abstract This study examines the effect of the anaesthetic agent propofol on the guinea pig ileum and whether this effect derives from an interaction of the drug with GABA receptors. Propofol produced a biphasic effect consisting of a dose-dependent contractile effect (EC 50 =2.2×10 −5 m ) followed by an `after relaxation'. This propofol effect was similar to the one produced by GABA and was bicuculline-sensitive (ID 50 =3.2×10 −7 m ). Propofol, at concentrations of 10 −7 and 10 −6 m , potentiated the ileum contractile responses to GABA, but only at the lower dose range of applied GABA, while at a concentration of 10 −5 m , it inhibited the contractile effect over the entire dose range of applied GABA. In addition, while the contractile response of the ileum to exogenously applied acetylcholine was not influenced by propofol at concentrations of up to 7×10 −6 m , it was antagonised by higher concentrations of propofol. In conclusion, the above data permit us to suggest that propofol's contractile effect on the guinea pig ileum is mediated by an interaction of the drug with GABA A -receptors.