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Picrotoxin and convulsant binding sites in mammalian brain

Olsen, R. W.; Leeb-Lundberg, F. LU and Napias, C. (1980) In Brain Research Bulletin 5(SUPPL. 2). p.217-221
Abstract

(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... (More)

(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.

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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Barbiturates, Benzodiazepines, Convulsants, GABA, Ionophores, Picrotoxin, Purines, Receptors
in
Brain Research Bulletin
volume
5
issue
SUPPL. 2
pages
217 - 221
publisher
Elsevier
external identifiers
  • scopus:0019137604
ISSN
0361-9230
DOI
10.1016/0361-9230(80)90037-4
language
English
LU publication?
no
id
c3c09624-70a3-4e73-9157-e270a562e209
date added to LUP
2019-06-12 12:02:35
date last changed
2019-09-27 13:56:19
@article{c3c09624-70a3-4e73-9157-e270a562e209,
  abstract     = {<p>(<sup>3</sup>H)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<sup>-</sup>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 (K<sub>d</sub> = 2μM) and B<sub>max</sub> 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 &lt;0.1μM, and also by 0.2 mM hypoxanthine and cytosine, but not nicotinamide, and by aqueous extracts of brain (40 μg protein, 10<sup>5</sup>x 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<sup>-</sup>channels?) in the opposite manner.</p>},
  author       = {Olsen, R. W. and Leeb-Lundberg, F. and Napias, C.},
  issn         = {0361-9230},
  keyword      = {Barbiturates,Benzodiazepines,Convulsants,GABA,Ionophores,Picrotoxin,Purines,Receptors},
  language     = {eng},
  month        = {01},
  number       = {SUPPL. 2},
  pages        = {217--221},
  publisher    = {Elsevier},
  series       = {Brain Research Bulletin},
  title        = {Picrotoxin and convulsant binding sites in mammalian brain},
  url          = {http://dx.doi.org/10.1016/0361-9230(80)90037-4},
  volume       = {5},
  year         = {1980},
}