Studies on the Gamma-Aminobutyric Acid Receptor/Ionophore Proteins in Mammalian Brain

  • R. W. Olsen
  • D. Greenlee
  • P. Van Ness
  • M. K. Ticku
Chapter
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 16)

Abstract

Receptor-ionophore proteins which mediate postsynaptic membrane responses to neurotransmitters can be studied in vitro by suitable radioactive ligand binding assays. Radioactive ligands are most appropriate when they act as potent and specific agonists or antagonists on the synapse under study. Drugs or toxins meeting these specifications are available for identification of numerous neurotransmitter receptors (Changeux et al., 1975; Cuatrecasas, 1974); in other cases binding of the radioactive neurotransmitter itself has been utilized (Snyder & Bennett, 1976). In very few cases have ligands been available for potential identification of elements other than the neurotransmitter recognition site (receptor) involved in mediating postsynaptic membrane responses (Young & Snyder, 1974; Bon & Changeux, 1975; Eldefrawi et al. 1977). Identification of binding sites in vitro as physiologically relevant postsynaptic receptor-ionophore proteins requires that numerous criteria be met, such as suitable quantity, binding affinity, tissue and subcellular location, and chemical specificity of the binding sites. In practice this last criterion demands quantitative estimates of dose-effect relationships for drugs active on the tissue under study and at least one such drug which is very specific for the receptor-ionophore as opposed to other potential binding proteins.

Keywords

Receptor Site Gaba Receptor Gaba Binding Nipecotic Acid Brain Regional Distribution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barker, J. L., MacDonald, R. L. and Ransom, B. R. 1977. Postsynaptic pharmacology of GABA on CNS neurons grown in tissue culture. In “Iontophoresis and Transmitter Mechanisms in the mammalian CNS”, (R. W. Ryall & J. S. Kelly, ed.) Elsevier, Amsterdam, in press.Google Scholar
  2. Beart, P. M. and Johnston, G. A. R. 1973. Transamination of analogues of γ-aminobutyric acid by extracts of rat brain mitochondria. Brain Res. 49: 459–462.PubMedCrossRefGoogle Scholar
  3. Birdsall, N. J. M. and Hulme, E. C. 1976. Biochemical studies on muscarinic acetylcholine receptors. J. Neurochem. 27: 7–16.PubMedCrossRefGoogle Scholar
  4. Bon, C. and Changeux, J.-P. 1975. Ceruleotoxin:an acidic neurotoxin from the venom of Bungarus caeruleus which blocks the response to a cholinergic agonist without binding to the cholingeric receptor site. FEBS Lett. 59: 212–216.PubMedCrossRefGoogle Scholar
  5. Bowery, N. G. and Dray, A. 1976. Barbiturate reversal of amino acid antagonism produced by convulsant agents. Nature 264: 276–278.PubMedCrossRefGoogle Scholar
  6. Bowery, N. G., Collins, J. F., Hill, R. G., Pearson, S. 1977. t- Butyl bicyclophosphate:a convulsant and GABA antagonist more potent than bicuculline. Br. J. Pharmacol. In press.Google Scholar
  7. Changeux, J.-P., Benedetti, L., Bourgeois, J.-P., Brisson, A., Cartaud, J., Devaux, P., Grunhagen, H., Moreau, M., Popot, J.-L., Sobel, A., and Weber, M. 1975. Some structural properties of the cholinergic receptor protein in its membrane environment relevant to its function as a pharmacological receptor. Cold Spring Harbor Symp. Quant. Biol. XL: 211–230.Google Scholar
  8. Coyle, J. T. and Enna, S. J. 1976. Neurochemical aspects of the ontogenesis of GABAnergic neurons in the rat brain. Brain Res. 111: 119–133.PubMedCrossRefGoogle Scholar
  9. Cuatrecasas, P. 1974. Membrane receptors. Ann. Rev. Biochem. 43: 168–214.CrossRefGoogle Scholar
  10. Curtis, D. R. and Johnston, G. A. R. 1974. Amino acid transmitters in the mammalian central nervous system. Ergebn. Physiol. 69: 98–188.Google Scholar
  11. DeBlas, A. and Mahler, H. R. 1976. Studies on nicotinic acetyl-choline receptors in mammalian brain, VI: isolation of a membrane fraction enriched in receptor function for different neurotransmitters. Biochem. Biophys. Res. Commun. 72: 24–32.CrossRefGoogle Scholar
  12. Dudel, J. and Hatt, H. 1976. Four types of GABA receptors in crayfish leg muscles characterized by desensitization and specific antagonists. Pflugers Arch. 364: 217–222.PubMedCrossRefGoogle Scholar
  13. Eldefrawi, A. T., Eldefrawi, M. E., Albuquerque, E. X., Oliveira, A. C., Mansour, N., Adler, M., Daly, J. W., Brown, G. B., Burgermeister, W., and Witkop, B. 1977. Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor. Proc. Nat. Acad. Sci. USA 74: 2172–2176.PubMedCrossRefGoogle Scholar
  14. Enna, S. J. and Snyder, S. H. 1975. Properties of γ-aminobutyric acid binding to receptor sites in rat central nervous system. Brain Res. 100: 81–97.PubMedCrossRefGoogle Scholar
  15. Enna, S. J. and Snyder, S. H. 1977. Influence of ions, enzymes, and detergents on GABA receptor binding in synaptic membranes of rat brain. Mol. Pharmacol. 13: 442–453.PubMedGoogle Scholar
  16. Enna, S. J., Collins, J. F. and Snyder, S. H. 1977. Stereospecificity and structure-activity required of GABA receptor binding in rat brain. Brain Res. 124: 185–190.PubMedCrossRefGoogle Scholar
  17. Gerschenfeld, H. M. 1973. Chemical transmission in invertebrate central nervous systems and neuromuscular junctions. Physiol. Rev. 53:1–119.Google Scholar
  18. Greenlee, D. V., VanNess, P. C. and Olsen, R. 1977. Gamma-amino-butyric acid receptor binding sites in membrane fractions from mammalian brain. Submitted.Google Scholar
  19. Iversen, L.L. and Kelly, J.S. 1975, Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells. Biochem. Pharmacol, 24: 933–938.PubMedCrossRefGoogle Scholar
  20. Jarboe, C.H., Porter, L.A. and Buckler, R.T., 1968. Structural aspects of picrotoxinin action. Med. Chem. 11: 729–731.CrossRefGoogle Scholar
  21. Johnston, G. A. R. 1978. Neuropharmacology of amino acid inhibitory transmitters. Ann. Rev. Pharmacol. Toxicol. 18: In press.Google Scholar
  22. Krnjevii, K. 1974. Chemical nature of synaptic transmission in vertebrates. Physiol. Rev. 54: 418–540.Google Scholar
  23. Krogsgaard-Larsen, P. and Johnston, G. A. R. 1975, Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J. Neurochem. 25: 797–802.PubMedCrossRefGoogle Scholar
  24. Krogsgaard-Larsen, P., Johnston, G. A. R., Curtis, D. R., Game, C. J. A. and McCulloch, R. M. 1975, Structure and biological activity of a series of con format ionally restricted analogues of GABA. J. Neurochem. 25: 803–809.PubMedCrossRefGoogle Scholar
  25. Lloyd, K. G., Shermen, L. and Hornykiewicz, O. 1977- Distribution of high affinity sodium-independent (3H) gamma-aminobutyric acid (GABA) binding in human brian: alterations in Parkinson’s disease. Brain Res. 127: 269 - 278.Google Scholar
  26. Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265–275.Google Scholar
  27. McLennan, H. 1973. y-Aminobutyric acid antagonists in crustacea. Can. J. Physiol. Pharmacol. 51: 774 - 775.Google Scholar
  28. Meiners, B., Kehoe, P., Shaner, D. M. and Olsen, R. W. 1978. Preparation of plasma membranes from crayfish muscle enriched in gamma-aminobutyric acid uptake and binding sites. Submitted Biochim. Biophys. Acta.Google Scholar
  29. Möhler, H. and Okada, T. 1977. GABA receptor binding with H(+) biculline methiodide in rat CNS. Nature 267: 65–67.PubMedCrossRefGoogle Scholar
  30. Möhler, H. and Okada, T. 1978. Properties of GABA receptor binding with 3H(+) bicuculline-methiodide in rat cerebellum. Mol. Pharmacol. In press.Google Scholar
  31. Olsen, R. W., Ban, M. and Miller, T. 1976. Studies on the neuropharmacological activity of bicuculline and related compounds. Brain Res. 102: 283–299.PubMedCrossRefGoogle Scholar
  32. Olsen, R. W., Ticku, M. K., Van Ness, P. C. and Greenlee, D. 1977. Effects of drugs on gamma-aminobutyric acid receptors, uptake, release, and synthesis in vitre. Brain Res. In press.Google Scholar
  33. Olsen, R. W., Mikoshiba, K. and Chanjeux, J.-P. 1978a. Gamma-cerebellum and depletion in agranular mutant mice. Submitted J. Neurochem.Google Scholar
  34. Olsen, R. W., Ticku, M. K. and Miller, T. 1978b. Dihydro-picrotoxinin binding to crayfish muscle sites possibly related to gamma-aminobutyric acid receptor-ionophores. Submitted Mol. Pharmacal.Google Scholar
  35. Simantov, R., Oster-granite, M. L., Herndon, R. M. and Snyder, S. H. 1976. Gamma-aminobutyric acid (GABA) receptor “binding selectively depleted by viral induced granule cell loss in hamster cerebellum. Brain Res. 105: 365–371.PubMedCrossRefGoogle Scholar
  36. Snyder, S. H. and Bennett, J. P. 1976. Neurotransmitter receptors in the brain. Ann. Rev. Physiol. 38: 153–175.CrossRefGoogle Scholar
  37. Takeuchi, A. and Takeuchi, N. 1969. A study of the action of picrotoxin on the inhibitory neuromuscular junction of the crayfish. J. Physiol. (London) 205: 377–391.Google Scholar
  38. Takeuchi, A. 1976. Studies of inhibitory effects of GABA on invertebrate nervous system. In “GABA in Nervous System Function” ( E. Roberts, T. N. Chase, and D. B. Tower, eds.) Raven Press, New York, pp. 255–267.Google Scholar
  39. Ticku, M. K. and Olsen, R. W. 1977a. γ-Aminobutyric acid-stimulated chloride permeability in crayfish muscle. Biochem. Biophys. Acta 464: 519–529.Google Scholar
  40. Ticku, M. K., Ban, M and Olsen, R. W. 1978b. Binding sites in rat brain for GABA synaptic antagonist, picrotoxin. Submitted.Google Scholar
  41. Ticky, M. K., Van Ness, P. C., Haycock, J. W., Levy, W. B. and Olsen, R. W. 1978b. Picrotoxinin binding sites in rat brain: regional distribution, and ontogeny, compared to GABA receptors. Submitted Brain Res.Google Scholar
  42. Van Ness, P. C., Greenlee, D. and Olsen, R. W. 1978. Gamma-amino-butyric acid binding sites in rat brain: comparison of sodium- dependent and -independent sites. In preparation.Google Scholar
  43. Wheal, H. V. and Kerkut, G. A. 1976. The action of muscimol on the inhibitory postsynaptic membranes of the crustacean neuromuscular junction. Brain Res. 109: 179–183.PubMedCrossRefGoogle Scholar
  44. Whittaker, V. P. and Barker, L. A. 1972. The subcellular fractionation of brain tissue with special reference to the preparation of synaptosomes and their component organelles. In “Methods in Neurochemistry”, Vol. 2. ( R. Fried, ed.) Marcel Dekker, New York, pp. 1–52.Google Scholar
  45. Wong, D. T. and Horng, J. S. 1977. Na-independent binding of GABA to the Triton X-100 treated synaptic membranes from cerebellum of rat brain. Life Sci. 20: 445–452.PubMedCrossRefGoogle Scholar
  46. Young, A. B. and Snyder, S. H. 1974. The glycine synaptic receptor: evidence that strychnine binding is associated with the ionic conductance mechanism. Proc. Nat. Acad. Sci. USA 71: 4002–4005.PubMedCrossRefGoogle Scholar
  47. Yarowsky, T. and Carpenter, D. O. 1976. A comparison of ionophores activated by acetylcholine and γ-aminobutyric acid in Aplysia neurons. Fed. Proc. Fed. Am. Soc. Exp. Biol. 35: 543.Google Scholar
  48. Zukin, S. R., Young, A. B. and Snyder, S. H. 1974. Gamma-aminobutyric acid binding to receptor sites in rat central nervous system. Proc. Nat. Acad. Sci. USA 71: 4802–4807.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • R. W. Olsen
    • 1
  • D. Greenlee
    • 1
  • P. Van Ness
    • 1
  • M. K. Ticku
    • 1
  1. 1.Department of BiochemistryUniversity of CaliforniaRiversideUSA

Personalised recommendations