Propofol's biphasic effect on GABA(A)-receptor-mediated response of the isolated guinea pig ileum

This study examines the effect of the anaesthetic agent propofol on the gui nea pig ileum and whether this effect derives from an interaction of the dr ug with GABA receptors. Propofol produced a biphasic effect consisting of a dose-dependent contractile effect (EC50 = 2.2 x 10(-5) M) followed by an ' after relaxation'. This propofol effect was similar to the one produced by GABA and was bicuculline-sensitive (ID50 = 3.2 X 10(-7) M). Propofol, at co ncentrations of 10(-7) and 10(-6) M, potentiatedthe ileum contractile respo nses 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 ent ire dose range of applied GABA. In addition, while the contractile response of the ileum to exogenously applied acetylcholine was not influenced by pr opofol at concentrations of up to 7 x 10(-6) M, it was antagonised by highe r concentrations of propofol. In conclusion, the above data permit us to su ggest that propofol's contractile effect on the guinea pig ileum is mediate d by an interaction of the drug with GABA(A)-receptors. (C) 1999 Academic P ress.