Detection of barbiturate-induced surface changes in cerebrocortical synaptosomes by phase partitioning in an aqueous two-phase system

Abstract

The barbiturates tested in this work (barbital, phenobarbital, thiopental and pentobarbital) modify the partition of synaptosomes in a Dextran T500-poly(ethylene glycol) 4000 two-phase system. Under adequate experimental conditions, the drugs increase the partition into the upper phase and this effect appears to be due to an action on the biological material and not on the interface potential of the system. This conclusion can be drawn from the fact that synaptosomes preincubated with low concentrations (0.1 mM) of barbital and pentobarbital maintained an increased partition into the upper phase. The extent of the effect observed appeared to be inversely proportional to the hydrophobicity of the drugs since phenobarbital and barbital showed a higher effect than thiopental and pentobarbital. Dithionite-induced anoxia, rotenone and ouabain also induced a similar increase of partition of synaptosomes into the upper phase, suggesting that the surface changes detected by phase partitioning modification of synaptosomes could be somehow related to the bioenergetic maintenance of the membrane ATPase.