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Possible Involvement of GABAA and GABAB Receptors in the Inhibitory Action of Lindane on Transmitter Release from Cerebellar Granule Neurons

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Abstract

Cerebellar granule cells in culture express receptors for GABA belonging to the GABAA and GABAB classes. In order to characterize the ability of the insecticide lindane to interact with these receptors cells were grown in either plain culture media or media containing 150 μM THIP as this is known to influence the properties of both GABAA and GABAB receptors. It was found that lindane regardless of the culture condition inhibited evoked (40 mM K+) release of neurotransmitter ([3H]D-aspartate as label for glutamate). In naive cells both GABAA and GABAB receptor active drugs prevented the inhibitory action of lindane but in THIP treated cultures none of the GABAA and GABAB receptor active drugs had any effect on the inhibitory action of lindane. This lack of effect was not due to inability of baclofen itself to inhibit transmitter release. It is concluded that lindane dependent on the state of the GABAA and GABAB receptors is able to indirectly interfere with both GABAA and GABAB receptors. In case of the latter receptors it was shown using [3H]baclofen to label the receptors that lindane could not displace the ligand confirming that lindane is likely to exert its action at a site different from the agonist binding site.

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Authors and Affiliations

  1. NeuroScience, PharmaBiotec Center, Dept. of Pharmacology, Royal Danish School of Pharmacy, DK-2100, Copenhagen, Denmark

    Inge Damgaard & Arne Schousboe (D.Sc.)

  2. Group of Neurochemistry, Central Res. Inst. for Chemistry, The Hungarian Academy of Sciences, H-1025, Budapest, Hungary

    Gabriella Nyitrai, Ilona Kovács & Julianna Kardos

  3. PharmaBiotec Res. Center, Dept. of Pharmacol., Royal Danish School of Pharmacy, Universitetsparken 2, Copenhagen, Denmark

    Arne Schousboe (D.Sc.)

Authors
  1. Inge Damgaard
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  2. Gabriella Nyitrai
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  3. Ilona Kovács
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  4. Julianna Kardos
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  5. Arne Schousboe
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Damgaard, I., Nyitrai, G., Kovács, I. et al. Possible Involvement of GABAA and GABAB Receptors in the Inhibitory Action of Lindane on Transmitter Release from Cerebellar Granule Neurons. Neurochem Res 24, 1189–1193 (1999). https://doi.org/10.1023/A:1020724823117

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