We have examined the effects of Na+ ions and 5'-guanylyl imidodiphosphate (Gpp(NH)p) on the equilibrium binding of dynorphin A and of a series of related agonist and antagonist peptides to kappa- and mu-opioid receptors in guinea pig (kappa) and rabbit (mu) cerebellum membrane preparations. The binding to kappa sites of dynorphin A and of the peptides displaying agonist properties was strongly inhibited in the presence of 120 mM NaCl and 50 microM Gpp(NH)p. In contrast, a somewhat lower sensitivity to the inhibitory effect of the two allosteric effectors was observed for the analogues of the series showing antagonist properties. The same general behavior, but more marked, was observed at mu sites, at both mu- and kappa-opioid receptors. The peptides had biochemical properties (binding sensitivity vs. insensitivity to sodium ions and guanine nucleotides) that correlated well with their biological activities (agonist vs. antagonist) previously determined in in vitro pharmacological bioassays.
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