Subcellular distribution of etorphine in rat brain and evidence for in vivo stereospecific binding

Control experiments were carried out by homogenizing rat brain at 0°C with sucrose containing various concentrations of [ ³H]-etrophine. Subcellular fractionation of this homogenate showed that the distribution of the labelled drug amongst the primary fractions was dependent on the concentration of etorphine in the homogenate. Rats were injected intravenously with 0.2 and 20 μg/kg of [ ³H]-etrophine. The brains were homogenized and fractionated in sucrose containing 4.2x10 ^-5M unlabelled etorphine in order to control redistribution artifacts. Different distribution profiles in the subcellular fractions were observed at these two dose levels. Concurrent administration of either cyprenorphine or naloxone with intravenous etorphine, caused a shift of the labelled drug from the P ₃ fraction to the supernatant fraction. The subcellular distribution of intravenously administered [ ³H]-etorphine was also studied by homogenizing brains in etrophine-free sucrose, and sucrose containing either levorphanol or dextrorphan. From these experiments it was concluded that the P ₃ microsomal fraction is a major site to which in vivo etorphine is stereospecifically bound in the rat brain.