Characterization of the selective inhibition of the delta subclass of opioid binding sites by alcohols

JM Hiller, LM Angel and EJ Simon

We recently reported that ethanol and other aliphatic alcohols exert a selective inhibition on the binding of enkephalins to delta opioid binding sites. We report here a more detailed investigation of the characteristics of this inhibition. Opioid binding sites of the kappa subtype are similar to mu opioid binding sites in their relative insensitivity to inhibition by aliphatic alcohols. Scatchard analysis of saturation data of enkephalin binding showed that inhibition is the result of a decrease in affinity. Results of kinetic experiments demonstrated that the inhibition can be entirely accounted for by an increase in the dissociation rate of the ligand-receptor complex. The presence of sodium ions in the incubation medium and raising the temperature of incubation exacerbate the inhibitory effectiveness of alcohols. The order of potency among structural isomers of alcohols for inhibition of delta receptor binding is as follows: straight-chain primary greater than isoprimary greater than secondary greater than tertiary. The order of inhibitory potency of the aliphatic alcohols tested correlates well with their ability to disorder the cell membrane lipid bilayer. It is suggested that this is a probable mechanism by which alcohols inhibit binding to delta opioid binding sites.

Volume 25, Issue 2, pp. 249-255, 03/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics