Enhancement of stereospecific opiate binding to neural membranes by phosphatidyl serine

Abstract

An effort was made to elucidate the possible involvement of phosphatidyl serine in the opiate receptor by examining stereospecific 3H-dihydromorphine binding to neural membrane preparations in the presence of exogenous phosphatidyl serine. The addition of phosphatidyl serine to suspensions of either synaptic membranes or a microsomal fraction significantly enhanced both high and lower affinity binding, the Kd's being 1.0 X 10(-9) and 5.7 X 10(-9) M without lipid and 5.0 X 10(-10) and 3.8 X 10(-9) M with added phosphatidyl serine. Phosphatidyl ethanolamine and lysophosphatidyl ethanolamine had an inhibitory effect on opiate binding. Sulfatides had a slight enhancing effect, while other acidic lipids and lecithin were without any effect. With the use of 3H-dansyl phosphatidyl serine it was established that sufficient exogenous lipid was associated with the membrane to account for the enhancement of opiate binding. The results were discussed from the standpoint of the modification of membrane lipids and their possible significance for the binding of opiates and other ligands. It is suggested that phosphatidyl serine may be an important component of the opiate pharmacophore.