Sodium regulation of agonist binding at opioid receptors. II. Effect of sodium replacement on opioid binding in guinea pig cortical membranes

Document Type

Journal Article

Publication Date



Molecular Pharmacology






The authors have examined the effects of sodium on the binding of opioid agonists to μ-, δ-, and κ-receptors in guinea pig cortical membranes. Concentration curves for sodium indicated that maximal inhibition of μ binding by this cation was about 60% and maximal inhibition for δ binding was about 70%, whereas that for κ binding was only about 20%. The concentration of sodium required for half-maximal inhibition of binding to all three sites was about 10-30 mM, corresponding to the intracellular sodium concentration. The nature of the sodium effect was further characterized by saturation analysis of binding to each of the three receptor types by comparing results obtained in the presence of 120 mM sodium with those obtained with equimolar replacement of sodium by another cation. Two radiolabeled agonists with different structural characteristics were tested for each binding site. In the presence of sodium, the affinity of the labeled agonists for μ sites was approximately 2-3-fold less than in its absence, but the density of binding sites was not changed. At κ sites, sodium reduced agonist affinity slightly but, again, did not alter the number of binding sites. In contrast, sodium reduced the apparent density of δ-binding sites while leaving the agonist affinity unchanged. Competition against antagonist binding to δ sites indicated that, in the presence of sodium, a higher proportion of sites was in a lower affinity state, as reflected by the biphasic nature of the agonist displacement curve. In contrast, the effect of sodium on displacement of antagonist from μ sites was to lower the affinity of the agonist. Competition against antagonist binding to κ sites also showed a reduction in agonist affinity by sodium, but no change in numbers of receptors. The results indicate that sodium may differentially regulate agonist binding to opioid receptor types and that this regulation may occur at an intracellular site. The κ site appears to be less sensitive to sodium than the μ and δ sites.

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