Skip to main content
NCBI home page
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
. 1979 Feb;76(2):977–981. doi: 10.1073/pnas.76.2.977

Identification of inosine and hypoxanthine as endogenous ligands for the brain benzodiazepine-binding sites.

T Asano, S Spector
PMCID: PMC383112  PMID: 284422

Abstract

Two endogenous ligands for the brain benzodiazepine-binding sites were isolated from bovine brain through gel filtration, paper electrophoresis, and paper chromatography. These ligands were identified as inosine and hypoxanthine, and both had a higher affinity for the brain benzodiazepine-binding sites than for benzodiazepine sites in some peripheral tissues. They did not bind to any other receptors tested, such as the opiate, muscarinic cholinergic, gamma-aminobutyric acid, and beta-adrenergic receptors. Both inosine and hypoxanthine competitively inhibited the binding of [3H]diazepam to the brain binding site.

Full text

PDF
977

Selected References

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

  1. Beer B., Chasin M., Clody D. E., Vogel J. R. Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety. Science. 1972 Apr 28;176(4033):428–430. doi: 10.1126/science.176.4033.428. [DOI] [PubMed] [Google Scholar]
  2. Braestrup C., Squires R. F. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3805–3809. doi: 10.1073/pnas.74.9.3805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bylund D. B., Snyder S. H. Beta adrenergic receptor binding in membrane preparations from mammalian brain. Mol Pharmacol. 1976 Jul;12(4):568–580. [PubMed] [Google Scholar]
  4. Dickman S. R., Harrison J. F., Grosser B. I. Decrease in adenyl nucleotide concentrations in rat brain components after footshock stress. Brain Res. 1973 Apr 27;53(2):483–487. doi: 10.1016/0006-8993(73)90238-2. [DOI] [PubMed] [Google Scholar]
  5. Drewes L. R., Gilboe D. D. Glycolysis and the permeation of glucose and lactate in the isolated, perfused dog brain during anoxia and postanoxic recovery. J Biol Chem. 1973 Apr 10;248(7):2489–2496. [PubMed] [Google Scholar]
  6. Enna S. J., Snyder S. H. GABA receptor binding in frog spinal cord and brain. J Neurochem. 1977 Apr;28(4):857–860. doi: 10.1111/j.1471-4159.1977.tb10639.x. [DOI] [PubMed] [Google Scholar]
  7. Gintzler A. R., Levy A., Spector S. Antibodies as a means of isolating and characterizing biologically active substances: presence of a non-peptide, morphine-like compound in the central nervous system. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2132–2136. doi: 10.1073/pnas.73.6.2132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Karobath M., Sperk G., Schönbeck G. Evidence for an endogenous factor interfering with 3H-diazepam binding to rat brain membranes. Eur J Pharmacol. 1978 Jun 1;49(3):323–326. doi: 10.1016/0014-2999(78)90111-5. [DOI] [PubMed] [Google Scholar]
  9. Kleihues P., Kobayashi K., Hossmann K. A. Purine nucleotide metabolism in the cat brain after one hour of complete ischemia. J Neurochem. 1974 Aug;23(2):417–425. doi: 10.1111/j.1471-4159.1974.tb04374.x. [DOI] [PubMed] [Google Scholar]
  10. Marangos P. J., Paul S. M., Greenlaw P., Goodwin F. K., Skolnick P. Demonstration of an endogenous, competitive inhibitor(s) of [3H] diazepam binding in bovine brain. Life Sci. 1978 Jun 5;22(21):1893–1900. doi: 10.1016/0024-3205(78)90476-9. [DOI] [PubMed] [Google Scholar]
  11. Möhler H., Okada T. Benzodiazepine receptor: demonstration in the central nervous system. Science. 1977 Nov 25;198(4319):849–851. doi: 10.1126/science.918669. [DOI] [PubMed] [Google Scholar]
  12. Möhler H., Okada T. Properties of 3H-diazepam binding to benzodiazepine receptors in rat cerebral cortex. Life Sci. 1977 Jun 15;20(12):2101–2110. doi: 10.1016/0024-3205(77)90191-6. [DOI] [PubMed] [Google Scholar]
  13. Pert C. B., Snyder S. H. Properties of opiate-receptor binding in rat brain. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2243–2247. doi: 10.1073/pnas.70.8.2243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peskar B., Spector S. Quantitative determination of diazepam in blood by radioimmunoassay. J Pharmacol Exp Ther. 1973 Jul;186(1):167–172. [PubMed] [Google Scholar]
  15. Squires R. F., Brastrup C. Benzodiazepine receptors in rat brain. Nature. 1977 Apr 21;266(5604):732–734. doi: 10.1038/266732a0. [DOI] [PubMed] [Google Scholar]
  16. Yamamura H. I., Snyder S. H. Muscarinic cholinergic binding in rat brain. Proc Natl Acad Sci U S A. 1974 May;71(5):1725–1729. doi: 10.1073/pnas.71.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zbinden G., Randall L. O. Pharmacology of benzodiazepines: laboratory and clinical correlations. Adv Pharmacol. 1967;5:213–291. doi: 10.1016/s1054-3589(08)60658-4. [DOI] [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