Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Apr;75(4):1713–1717. doi: 10.1073/pnas.75.4.1713

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

Arthur J Blume 1
PMCID: PMC392409  PMID: 205867

Abstract

This study shows that nucleotides, as well as ions, regulate the opiate receptors of brain. GMP-P(NH)P and Na+ reduce the amount of steady-state specific [3H]dihydromorphine binding and increase the rate of dissociation of the ligand from the opiate receptor. In contrast, Mn2+ decreases the rate of ligand dissociation and antagonizes the ability of Na+ to increase dissociation. The effects of GMP-P(NH)P on steady-state binding and dissociation are not reversed by washing. Only GTP, GDP, ITP, and IMP-P(NH)P, in addition to GMP-P(NH)P, increase the rate of dihydromorphine dissociation. The site of nucleotide action appears to have high affinity: <1 μM GMP-P(NH)P produces half-maximal increases in ligand dissociation. GMP-P(NH)P- and Na+-directed increases in dissociation have also been 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 have been found for the agonist [3H]-etorphine and the antagonist [3H]naltrexone. Although the plasma membrane receptors for a number of other neuro-transmitters and hormones are also regulated by guanine nucleotides, the opiate receptors appear unique because only they show nucleotide regulation of both agonist and antagonist binding.

Keywords: GMP-P(NH)P, agonists, antagonists

Full text

PDF
1713

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Birnbaumer L., Pohl S. L., Rodbell M. Adenyl cyclase in fat cells. 1. Properties and the effects of adrenocorticotropin and fluoride. J Biol Chem. 1969 Jul 10;244(13):3468–3476. [PubMed] [Google Scholar]
  2. Birnbaumer L., Pohl S. L., Rodbell M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. II. Comparison between glucagon- and fluoride-stimulated activities. J Biol Chem. 1971 Mar 25;246(6):1857–1860. [PubMed] [Google Scholar]
  3. Birnbaumer L., Pohl S. L., Rodbell M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. II. Comparison between glucagon- and fluoride-stimulated activities. J Biol Chem. 1971 Mar 25;246(6):1857–1860. [PubMed] [Google Scholar]
  4. Goldstein A., Cox B. M., Klee W. A., Nirenberg M. Endorphin from pituitary inhibits cyclic AMP formation in homogenates of neuroblastoma X glioma hybrid cells. Nature. 1977 Jan 27;265(5592):362–363. doi: 10.1038/265362a0. [DOI] [PubMed] [Google Scholar]
  5. Kebabian J. W., Zatz M., Romero J. A., Axelrod J. Rapid changes in rat pineal beta-adrenergic receptor: alterations in l-(3H)alprenolol binding and adenylate cyclase. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3735–3739. doi: 10.1073/pnas.72.9.3735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kimura N., Nagata N. The requirement of guanine nucleotides for glucagon stimulation of adenylate cyclase in rat liver plasma membranes. J Biol Chem. 1977 Jun 10;252(11):3829–3835. [PubMed] [Google Scholar]
  7. Klee W. A., Nirenberg M. Mode of action of endogenous opiate peptides. Nature. 1976 Oct 14;263(5578):609–612. doi: 10.1038/263609a0. [DOI] [PubMed] [Google Scholar]
  8. Lad P. M., Welton A. F., Rodbell M. Evidence for distinct guanine nucleotide sites in the regulation of the glucagon receptor and of adenylate cyclase activity. J Biol Chem. 1977 Sep 10;252(17):5942–5946. [PubMed] [Google Scholar]
  9. Lad P. M., Welton A. F., Rodbell M. Evidence for distinct guanine nucleotide sites in the regulation of the glucagon receptor and of adenylate cyclase activity. J Biol Chem. 1977 Sep 10;252(17):5942–5946. [PubMed] [Google Scholar]
  10. Lefkowitz R. J., Mullikin D., Wood C. L., Gore T. B., Mukherjee C. Regulation of prostaglandin receptors by prostaglandins and guanine nucleotides in frog erythrocytes. J Biol Chem. 1977 Aug 10;252(15):5295–5303. [PubMed] [Google Scholar]
  11. Lefkowitz R. J. Stimulation of catecholamine-sensitive adenylate cyclase by 5'-guanylyl-imidodiphosphate. J Biol Chem. 1974 Oct 10;249(19):6119–6124. [PubMed] [Google Scholar]
  12. Londos C., Rodbell M. Multiple inhibitory and activating effects of nucleotides and magnesium on adrenal adenylate cyclase. J Biol Chem. 1975 May 10;250(9):3459–3465. [PubMed] [Google Scholar]
  13. Londos C., Salomon Y., Lin M. C., Harwood J. P., Schramm M., Wolff J., Rodbell M. 5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3087–3090. doi: 10.1073/pnas.71.8.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maguire M. E., Van Arsdale P. M., Gilman A. G. An agonist-specific effect of guanine nucleotides on binding to the beta adrenergic receptor. Mol Pharmacol. 1976 Mar;12(2):335–339. [PubMed] [Google Scholar]
  15. Mukherjee C., Lefkowitz R. J. Desensitization of beta-adrenergic receptors by beta-adrenergic agonists in a cell-free system: resensitization by guanosine 5'-(beta, gamma-imino)triphosphate and other purine nucleotides. Proc Natl Acad Sci U S A. 1976 May;73(5):1494–1498. doi: 10.1073/pnas.73.5.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pasternak G. W., Snowman A. M., Snyder S. H. Selective enhancement of [3H]opiate agonist binding by divalent cations. Mol Pharmacol. 1975 Nov;11(6):735–744. [PubMed] [Google Scholar]
  17. Pasternak G. W., Snyder S. H. Identification of novel high affinity opiate receptor binding in rat brain. Nature. 1975 Feb 13;253(5492):563–565. doi: 10.1038/253563a0. [DOI] [PubMed] [Google Scholar]
  18. Pert C. B., Pasternak G., Snyder S. H. Opiate agonists and antagonists discriminated by receptor binding in brain. Science. 1973 Dec 28;182(4119):1359–1361. doi: 10.1126/science.182.4119.1359. [DOI] [PubMed] [Google Scholar]
  19. Pfeuffer T., Helmreich E. J. Activation of pigeon erythrocyte membrane adenylate cyclase by guanylnucleotide analogues and separation of a nucleotide binding protein. J Biol Chem. 1975 Feb 10;250(3):867–876. [PubMed] [Google Scholar]
  20. Rodbell M., Lin M. C., Salomon Y. Evidence for interdependent action of glucagon and nucleotides on the hepatic adenylate cyclase system. J Biol Chem. 1974 Jan 10;249(1):59–65. [PubMed] [Google Scholar]
  21. Schreier M. H., Noll H. Conformational changes in ribosomes during protein synthesis. Proc Natl Acad Sci U S A. 1971 Apr;68(4):805–809. doi: 10.1073/pnas.68.4.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharma S. K., Nirenberg M., Klee W. A. Morphine receptors as regulators of adenylate cyclase activity. Proc Natl Acad Sci U S A. 1975 Feb;72(2):590–594. doi: 10.1073/pnas.72.2.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simantov R., Snowman A. M., Snyder S. H. Temperature and ionic influences on opiate receptor binding. Mol Pharmacol. 1976 Nov;12(6):977–986. [PubMed] [Google Scholar]
  24. Simantov R., Snyder S. H. Morphine-like peptides, leucine enkephalin and methionine enkephalin: interactions with the opiate receptor. Mol Pharmacol. 1976 Nov;12(6):987–998. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES