Picrotoxin and convulsant binding sites in mammalian brain
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(3H)α-Dihydropicrotoxinin (DHP) binds to membrane sites in mammalian brain which appear to be related to the convulsant action of picrotoxin at the level of membrane Cl-channels which are at least partially regulated by the inhibitory neurotransmitter GABA. DHP binding to rat cerebral cortex (assayed by centrifugation) showed a single class of sites (Kd = 2μM) and Bmax of 4 pmol/mg protein, and was competitively inhibited by depressant barbiturates (1-10μM), excitatory barbiturates (10-100 nM), and cage convulsants, e.g. bicyclophosphates (1-10 μM), but not by GABA or related compounds. DHP binding was stereospecifically and potently inhibited by pyrethroid insecticides (10-1000 nM), by depressant benzodiazepines (0.5-50 μM), and excitatory benzodiazepines (e.g. RO5-3663) at <0.1μM, and also by 0.2 mM hypoxanthine and cytosine, but not nicotinamide, and by aqueous extracts of brain (40 μg protein, 105x g supernatant) at 0° without preincubation. These or related substances may be endogenous ligands for the receptor sites which bind picrotoxin and other convulsants. Anticonvulsants may act at the same site (Cl-channels?) in the opposite manner.
Ämnesklassifikation (UKÄ) – OBLIGATORISK
|Tidskrift||Brain Research Bulletin|
|Utgåva nummer||SUPPL. 2|
|Status||Published - 1980 jan 1|
|Peer review utförd||Ja|