GABA and picrotoxinin receptors in clonal nerve cells

Abstract

γAminobutyric acid (GABA) is a neurotransmitter which seems to mediate inhibitory synaptic transmission in many regions of the central nervous system (CNS) of vertebrates and invertebrates1. GABA has been shown to act by increasing membrane chloride permeability in invertebrate muscle2,3, and a similar mechanism has been suggested for the vertebrate CNS4. The response to GABA is inhibited noncompetitively by the convulsant picrotoxinin1–5. Binding sites for radioactive GAB A6–8 and picrotoxinin9–11 (the active component of picrotoxin) have been described in homogenates of invertebrate muscle and mammalian CNS; these binding sites show many properties expected of postsynaptic membrane macromolecules involved in the receptor-ionophore function of GABA. Nevertheless, unambiguous correlation between biochemical assays and in vivo function is difficult to obtain, especially in heterogeneous tissue such as mammalian CNS. One approach to this problem involves cloned cell lines of neuronal origin which retain in culture the differentiated function to be studied (see, for example, ref. 12). Certain cell lines cloned from rat13 and mouse14 nervous system possess neuronal properties such as electrical excitability, neurotransmitter synthetic enzymes12, neurotransmitter uptake15,16, binding of defined ligands to their appropriate neurotransmitter receptors12,17,18, and receptor-coupled responses to neurotransmitters17,19,20. Several cell lines of apparent glial origin have also been described13,21,22. To determine whether binding sites for GABA and picrotoxinin are localised to nerve cells, a variety of clonal cell lines were assayed for their ability to bind those ligands. We report here the presence of GABA and picrotoxinin binding sites with receptor-like properties in several clonal nerve cell lines obtained from the rat CNS, and the absence of such binding sites in many other cell lines of non-neuronal origin.

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References

  1. 1

    Roberts, E., Chase, T. N. & Tower, D. B. GABA in Nervous System Function (Raven, New York, 1976).

  2. 2

    Takeuchi, A. & Takeuchi, N. J. Physiol., Lond. 216, 391–401 (1971).

  3. 3

    Ticku, M. K. & Olsen, R. W. Biochim. biophys. Acta 464, 519–529 (1977).

  4. 4

    Krnjevic, K. Physiol. Rev. 54, 418–540 (1974).

  5. 5

    Johnston, G. A .R. A. Rev. Pharmac. Tox. 18, 269–289 (1978).

  6. 6

    Zukin, S. R., Young, A. B. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 71, 4802–4807 (1974).

  7. 7

    Greenlee, D. V., Van Ness, P. C. & Olsen, R. W. J. Neurochem. 31, 933–938 (1978).

  8. 8

    Greenlee, D. V., Van Ness, P. C. & Olsen, R. W. Life Sci. 22, 1653–1662 (1978).

  9. 9

    Olsen, R. W., Ticku, M. K. & Miller, T. Molec. Pharmac. 14, 381–390 (1978).

  10. 10

    Ticku, M. K., Ban, M. & Olsen, R. W. Molec. Pharmac. 14, 391–402 (1978).

  11. 11

    Ticku, M. K. & Olsen, R. W. Life Sci. 22, 1643–1652 (1978).

  12. 12

    Patrick, J., Heineraann, S. & Schubert, D. A. Rev. Neurosci. 1, 417–443 (1978).

  13. 13

    Schubert, D. et al. Nature 249, 224–227 (1974).

  14. 14

    Augusti-Tocco, G. & Sato, G. Proc. natn. Acad. Sci. U.S.A. 64, 311–315 (1969).

  15. 15

    Hutchinson, H. T., Werrback, K., Vance, C. & Haber, B. Brain Res. 66, 265–274 (1974).

  16. 16

    Schubert, D. Brain Res. 84, 87–98 (1975).

  17. 17

    Strange, P. C., Birdsall, N. J. M. & Burgen, A. S. V. Biochem. Soc. Trans. 5, 189–191 (1977).

  18. 18

    Burgermeister, W., Klein, W. L., Nirenberg, M. & Witkop, B. Molec. Pharmac. 14, 751–767 (1978).

  19. 19

    Stallcup, W. B. & Cohn, M. Expl Cell Res. 98, 277–284 (1976).

  20. 20

    Richelson, E., Prendergast, F. G. & Divinetz-Romero, S. Biochem. Pharmac. 27, 2039–2048 (1978).

  21. 21

    Benda, P., Lightbody, J., Sato, G., Levine, L. & Sweet, W. Science 161, 370–371 (1968).

  22. 22

    Schubert, D., Carlisle, W. & Look, C. Nature 254, 341–343 (1975).

  23. 23

    Enna, S. J. & Snyder, S. H. Brain Res. 100, 81–97 (1975).

  24. 24

    Ticku, M. K., Van Ness, P. C., Haycock, J., Levy, W. B. & Olsen, R. W. Brain Res. 150, 642–647 (1978).

  25. 25

    Van Ness, P. C. & Olsen, R. W. J. Neurochem. 33, 593–596 (1979).

  26. 26

    Guidotti, A., Toffano, G. & Costa, E. Nature 275, 553–555 (1978).

  27. 27

    Green, L. A. & Tischler, A. S. Proc. natn. Acad. Sci. U.S.A. 73, 2424–2428 (1976).

  28. 28

    Yaffe, D. Proc. natn. Acad. Sci. U.S.A. 61, 477–481 (1968).

  29. 29

    Horibata, K. & Harris, A. Expl Cell Res. 60, 61–77 (1970).

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Napias, C., Olsen, R. & Schubert, D. GABA and picrotoxinin receptors in clonal nerve cells. Nature 283, 298–299 (1980). https://doi.org/10.1038/283298a0

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