Enhancement of opiate binding to neural membranes with an ethyl glycolate ester of phosphatidyl serine

In order to elucidate the mechanism by which acidic lipids enhance the stereospecific high-affinity binding of opiates to neural membranes, chemical synthesis and testing of modified lipid derivatives were undertaken. Phosphatidyl serine ethyl glycolate ester was synthesized from phosphatidyl serine (PS) and ethyl diazoacetate and purified by preparative TLC on silica gel. The PS ester enhanced the specific binding of ³H]dihydromorphine to synaptic membranes from rat brain by 26%, while the enhancement with PS was 35% over control without added lipid. In contrast to PS, there was no complex formation between the PS ester and opiates or Ca²⁺, ruling out these possible mechanisms. It is suggested that acidic lipids enhance opiate binding by a direct interaction with the receptor.