Effects of Ethanol, Temperature, and Endogenous Regulatory Factors on the Characteristics of Striatal Opiate Receptors

Ethanol can alter the affinity of mouse striatal opiate receptors for their ligands, and the present studies were aimed at determining the importance of the receptor microenvironment for this effect of ethanol. Changing the temperature of the binding assay, and thus altering the properties of neuronal membrane lipids, resulted in changes in the observed affinity of striatal binding sites for dihydromorphine (DHM), but not for D-Ala2, D-Leu5-enkephalin (ENK). The changes in temperature also differentially altered the response of the two binding sites to ethanol. Two other factors that regulate opiate receptor affinity, Na+ and GTP, also affected the response to ethanol. High concentrations of ethanol were more effective at decreasing receptor affinity for both DHM and ENK when the binding assays were performed in the presence of GTP or Na+. In addition, at 37 degrees C and in the presence of GTP or Na+, DHM binding, but not ENK binding, was significantly inhibited by a low, physiologically attainable concentration of ethanol. Our results suggest that the response of opiate receptors to ethanol is influenced by the microenvironment of the receptors, including the physical state of the membrane lipids and/or by the nature of the interactions of receptors with "coupling proteins" within the membrane. The differential responses of mu and delta receptors to temperature and to ethanol suggest that these receptors reside in specific membrane environments. Under physiological conditions, several different factors may contribute to a selective action of ethanol on particular subtypes of opiate receptors.