Roles of Synaptic Membranous Phospholipids in the Modulation of Cerebral GABA and Benzodiazepine Receptor Bindings

  • Kinya Kuriyama
  • Yukio Yoneda
Part of the Experimental and Clinical Neuroscience book series (ECN)


It has been well established that ϒ-aminobutyric acid (GABA) plays an inhibitory neurotransmitter role in the mammalian central nervous system (CNS) (Kuriyama et al., 1966: Iversen and Bloom, 1972: Yoneda and Kuriyama, 1978) as well as in the invertebrate nervous system (Kravitz et al., 1965). The specific binding of [3H] GABA to synaptic membrane preparations obtained from the rat brain has been thought to reflect the association of this neuroactive amino acid with its physiologically relevant synaptic receptors (Zukin et al., 1974: Enna and Snyder, 1977). Recently, it has been also demonstrated that muscimol, which is isolated from the mushroom Amanita muscaria, has a potent agonistic action on synaptic GABA receptors (Krogsgaard-Larsen et al., 1976), and [3H] muscimol is usable as a specific radioligand for biochemical (Beaumont et al., 1978; Snodgrass, 1978) as well as autoradiographic (Chan-Palay, 1979) studies on GABA receptors in the mammalian CNS. In addition, muscimol is known to be a more potent agonist than GABA itself in terms of the Induction of conductance changes at the crustacean inhibitory synapses (Hori et al., 1978)


Gaba Receptor Synaptic Membrane Mammalian Central Nervous System Diazepam Binding Fatty Acid Anion 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Asano T and Ogasawara N (1980) Solubilization of ϒ-amino- butyric acid receptor from rat brain., Life Sci. 26, 1131–1137.PubMedCrossRefGoogle Scholar
  2. Beaumont K, Chilton W, Yamamura HI, and Enna SJ (1978) Muscimol binding in rat brain: Association with synaptic GABA receptors. Brain Res. 148, 153–162.Google Scholar
  3. Braestrup C and Squires RF (1977) Specific benzodiazepine receptors in rat brain characterized by high affinity [3H] diazepam binding., Proc. Natl. Acad. Sci. USA 74, 3805–3809.PubMedCrossRefGoogle Scholar
  4. Brilely MS and Langer SZ (1978) Influence of GABA receptor agonists and antagonists on the binding of [3H] diazepam to the benzodiazepine receptor., Eur. J. Pharmacol. 52, 129–132.CrossRefGoogle Scholar
  5. Chan-Palay V (1979) Autoradiographic localization of ϒ-aminobutyric acid receptors in the rat central nervous system by using [3H] muscimol., Proc. Natl. Acad. Sci. USA 75, 1024–1028.CrossRefGoogle Scholar
  6. Costa E, Guidotti A, Mao CC, and Suria A (1975) New concepts on the mechanism of action of benzodiazepines. Life Sci. 17, 167–186.PubMedCrossRefGoogle Scholar
  7. Costa T, Rodbard D, and Pert CB (1979) Is the benzo-diazepine receptor coupled to a chloride anion channel? Nature 277, 315–317.PubMedCrossRefGoogle Scholar
  8. Eccles JC (1964) in The Physiology of Synapses (Eccles JC, ed), Academic Press, New York.CrossRefGoogle Scholar
  9. Enna SJ and Snyder SH (1976) Influences of ions, enzymes and detergents on ϒ-aminobutyric acid receptor binding in synaptic membranes of rat brain., Mol. Pharmacol. 13, 442–453.Google Scholar
  10. Gallager DW (1978) Benzodiazepines: potentiation of a GABA inhibitory response on the dorsal raphe nucleus. Eur. J. Pharmacol. 49, 133–143.PubMedCrossRefGoogle Scholar
  11. Gavish M and Snyder SH (1981) Y-Aminobutyric acid and benzodiazepine receptors: Copurification and characterization. Proc. Natl. Acad. Sci. USA 78, 1939–1942.PubMedCrossRefGoogle Scholar
  12. Giambalvo CT and Rosenberg P (1976) The effect of phospho-lipases and proteases on the binding of ϒ-aminobutyric acid to junctional complexes of rat cerebellum. Biochim. Biophys. Acta 436, 741–756.PubMedCrossRefGoogle Scholar
  13. Goodman DS (1958) The interaction of human serum albumin with long-chain fatty acid anions. J. Am. Chem. Soc. 80, 3892–3898CrossRefGoogle Scholar
  14. Greenlee DV, Van Ness PG, and Olsen RW (1978) Endogenous inhibitor of GABA binding in mammalian brain., Life Sci. 22, 1953–1962.CrossRefGoogle Scholar
  15. Hori N, Ikeda K, and Roberts E (1978) Muscimol, GABA, picrotoxin: effects on membrane conductance of a crustacean neuron. Brain Res. 141, 364–370.PubMedCrossRefGoogle Scholar
  16. Ito Y, Kuriyama K, Ueno E, Nishimura C, and Yoneda Y (1982) Solubilization and partial purification of cerebral GABA receptors, in Problems in GABA Research ( Okada Y, and Roberts E, eds), pp 316–327, Excerpta. Medica, Amsterdam.Google Scholar
  17. Ito Y and Kuriyama K (1982) Some properties of solubilized GABA receptor. Brain Res. 236, 351–363.PubMedCrossRefGoogle Scholar
  18. Iversen LL and Bloom FE (1972) Studies on the uptake of [3H]GABA and [3H ]glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography. Brain Res. 41, 131–143.PubMedCrossRefGoogle Scholar
  19. Johnston GAR and Kennedy SME (1978) GABA receptor and phospholipids, in Amino Acids as Chemical Transmitters ( Fonnum F, ed), pp 507–516, Plenum Press, New York.Google Scholar
  20. Karobath M and Sperk G (1979) Stimulation of benzodiazepine receptor binding by ϒ-aminobutyric acid., Proc. Natl. Acad. Sci. USA 76, 1004–1006.PubMedCrossRefGoogle Scholar
  21. Kravitz EA, Morinoff PB, and Hall ZW (1965) A comparison of the enzymes and substrates of gamma-aminobutyric acid metabolism in lobster excitatory and inhibitory axons., Proc. Natl. Acad. Sci. USA 54, 778–782.Google Scholar
  22. Krogsgaard-Larsen P, Johnston GAR, Curtis DR, Game CJA, and McCullock RH (1976) Structure and biological activity of a series of conformationally restricted analogues of GABA. J. Neurochem. 25, 803–809.CrossRefGoogle Scholar
  23. Kuriyama K, Haber B, Sisken B, and Roberts E (1966) The ϒ-aminobutyric acid system in rabbit cerebellum. Proc. Natl. Acad. Sci. USA 55, 846–852.Google Scholar
  24. Kuriyama K, Kurihara E,Ito Y, and Yoneda Y (1980) Increase in striatal [3H]muscimol binding following intrastriatal injection of kainic acid: A denervation supersensitivity phenomenon. J. Neurochem. 35, 343–348.Google Scholar
  25. Lloyd KG and Davidson L (1979) [3H] GABA binding in brains from Huntington’s chorea patients: Altered regulation by phospholipids?, Science 205, 1147–1149.Google Scholar
  26. Möhler H and Okada T (1977) Benzodiazepine receptors: demonstration in the central nervous system. Science 198, 849–851.PubMedCrossRefGoogle Scholar
  27. Möhler H, Okada T, Heity PH, and Ulrich J (1978) Bio-chemical identification of the site of action of benzo-diazepines in human brain by [3H] diazepam binding., Life Sci. 22, 985–996.PubMedCrossRefGoogle Scholar
  28. Snodgrass SR (1978) Use of [3H] Jmuscimol for GABA receptor studies. Nature 273, 392–394.PubMedCrossRefGoogle Scholar
  29. Squires RF and Braestrup C (1977) Benzodiazepine receptors in rat brain., Nature 266, 732–734.PubMedCrossRefGoogle Scholar
  30. Stephenson FA, Watkins AE, and Olsen RW (1982) Physio-chemical characterization of detergent-solubilized ϒ-aminobutyric acid and benzodiazepine receptor proteins from bovine brain., Eur. J. Biochem. 123, 291–298.Google Scholar
  31. Tallman JF, Thomas JW, and Gallager DW (1978) GABAergic modulation of benzodiazepine binding site sensitivity., Nature 274, 383–385.PubMedCrossRefGoogle Scholar
  32. Toffano G, Guidotti A, and Costa E (1978) Purification of an endogenous protein inhibitor on the high affinity binding of ϒ-aminobutyric acid to synaptic membranes of rat brain., Proc. Natl. Acad. Sci. USA 75, 4024–4028.Google Scholar
  33. Ueno E and Kuriyama K (1981) Phospholipids and benzodiazepine recognition sites of brain synaptic membranes., Neuropharmacol. 20, 1169 - 1176.CrossRefGoogle Scholar
  34. Wolfe LS (1982) Eicosanoids: prostaglandins, thromboxanes, leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids. J. Neurochem. 38, 1–14.PubMedCrossRefGoogle Scholar
  35. Yoneda Y and Kuriyama K (1978) A comparison of microdistributions of taurine and cysteine sulphinate decarboxylase activity with those of GABA and L-glutamate decarboxylase activity in rat spinal cord and thalamus., J. Neurochem. 30, 821–825.PubMedCrossRefGoogle Scholar
  36. Yoneda Y and Kuriyama K (1980a) Some characteristics of [3H] muscimol binding to synaptic membrane from rat brain. Brain Res. 197, 554–560.PubMedCrossRefGoogle Scholar
  37. Yoneda Y and Kuriyama K (1980b) Presence of a low molecular weight endogenous inhibitor on 3H-muscimol binding in synaptic membranes., Nature 285, 670–673.PubMedCrossRefGoogle Scholar
  38. Zukin SR, Ydung AB, and Snyder SH (1974) Gamma-amino- butyric acid binding to receptor sites in the rat central nervous system. Proc. Natl. Acad. Sci. USA 71, 4802–4807Google Scholar

Copyright information

© The Humana Press Inc. 1983

Authors and Affiliations

  • Kinya Kuriyama
    • 1
  • Yukio Yoneda
    • 1
  1. 1.Department of PharmacologyKyoto Prefectural University of MedicineKyotoJapan

Personalised recommendations