Effect of ethanol on the binding of conformationally rigid and labile ligands of opioid receptors to rat brain membranes.

The effect of ethanol on the binding of conformationally rigid and labile ligands for mu and delta opioid receptors to rat brain membranes was determined. The mu ligands used for the studies were [3H]naltrexone and [3H]Tyr-D-Ala-Gly-N-MePhe-Gly-ol (DAGO), and delta ligands used were [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr-OH (DSTLE) and [3H]Tyr-D-Ala-Gly-Phe-Leu (DADLE). The binding of all the opioid ligands was inhibited by ethanol in a concentration-dependent manner. For mu ligands the inhibition was greater for [3H]DAGO binding than for the binding of [3H]naltrexone. For delta ligands, the inhibition by ethanol of the binding of [3H]DADLE was greater than that of [3H]DSTLE. Fourier-transform infrared (FT-IR) spectroscopy was used to determine the conformation of opioid peptides. The data indicated that the conformation of peptides was altered in the presence of ethanol. The results suggest that ethanol inhibits the binding of both mu and delta opioid ligands with greater inhibition observed with conformationally labile ligands. Finally, the alteration in the conformation of the peptide ligands by ethanol, in addition to denaturation of the receptor protein, may also account for the observed inhibitory effect of ethanol on brain opioid receptors.