Possible involvement of GABA(A) and GABA(B) receptors in the inhibitory action of lindane on transmitter release from cerebellar granule neurons.
Cerebellar granule cells in culture express receptors for GABA belonging to the GABA(A) and GABA(B) 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 microM THIP as this is known to influence the properties of both GABA(A) and GABA(B) 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 GABA(A) and GABA(B) receptor active drugs prevented the inhibitory action of lindane but in THIP treated cultures none of the GABA(A) and GABA(B) 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 GABA(A) and GABA(B) receptors is able to indirectly interfere with both GABA(A) and GABA(B) 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.
Damgaard
I
I
NeuroScience, PharmaBiotec Center, Dept. of Pharmacology, Royal Danish School of Pharmacy, Copenhagen.
Nyitrai
G
G
Kovács
I
I
Kardos
J
J
Schousboe
A
A
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001418:Baclofen / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D001224:Aspartic Acid; D001556:Hexachlorocyclohexane; D001418:Baclofen