Interaction of ligands with the opiate receptors of brain membranes: Regulation by ions and nucleotides

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Abstract
Nucleotides, as well as ions, regulated the opiate receptors of rat brain. GMP-P(NH)P and Na+ reduced the amount of steady-state specific [3H]dihydromorphine binding and increased the rate of dissociation of the ligand from the opiate receptor. In contrast, Mn2+ decreased the rate of ligand dissociation and antagonized the ability of Na+ to increase dissociation. The effects of GMP-P(NH)P on steady-state binding and dissociation were not reversed by washing. Only GTP, GDP, ITP and IMP-P(NH)P, in addition to GMP-P(NH)P, increased the rate of dihydromorphine dissociation. The site of nucleotide action had high affinity: < 1 .mu.M GMP-P(NH)P produced half-maximal increases in lignad dissociation. GMP-P(NH)P- and Na+-directed increases in dissociation were also found for the opiate agonists [3H]etorphine, [3H]Leu-enkephalin, and [3H]Met-enkephalin and the opiate antagonist [3H]naltrexone. Mn2+-directed decreases in dissociation were found for the agonist [3H]etorphine and the antagonist [3H]naltrexone. Although the plasma membrane receptors for a number of other neurotransmitters and hormones were also regulated by guanine nucleotides, the opiate receptors appearred unique because only they showed nucleotide regulation of both agonist and antagonist binding.

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