Abstract: Guanine nucleotides differentiate binding of tritium‐labeled agonists and antagonists to rat brain membranes. In the absence of sodium, GTP (50 μM) decreased binding of [3H]‐labeled agonists by 20–60% and [3H]‐labeled antagonists by 0–20%. In the presence of 100 mM‐NaCl, GTP had no effect on antagonist binding, but decreased agonist binding by 60–95%. GMP was less potent than either GTP or GDP in decreasing agonist binding. GTP (50 μM) reduced high‐affinity [3H]dihydromorphine sites by 52% and low‐affinity sites by 55%. Without sodium, GTP reduced high‐affinity [3H]‐naloxone sites by 36%; in the presence of 100 mM‐NaCl, GTP had no effect on either high‐ or low‐affinity [3H]naloxone sites. GTP increased the association rate of [3H]dihydromorphine twofold and the dissociation rate by fourfold, while having no effect on association or dissociation rates of the antagonist [3H]diprenorphine. The affinities of uniabeled antagonists in inhibiting [3H]‐diprenorphine binding were not affected by GTP or sodium, but the affinities of agonists were reduced 40‐ 120‐fold, with met‐ and leu‐enkephalin affinities reduced by the greatest degree. GTP and sodium lowered [3H]dihydromorphine binding in an additive fashion, while divalent cations, especially manganese, reversed the effects of GTP on [3H]‐labeled agonist binding by stimulating membrane‐bound phosphatases that hydrolyze GTP to GMP and guanosine. These results suggest that by affecting binding of agonists, but not antagonists, GTP may regulate opiate receptor interactions with their physiological effectors.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Neurochemistry|
|State||Published - Mar 1980|
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience