Picrotoxin and convulsant binding sites in mammalian brain
(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.
(Less)
- author
- Olsen, R. W. ; Leeb-Lundberg, F. LU and Napias, C.
- publishing date
- 1980-01-01
- 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
- 2021-01-03 08:45:40
@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 <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}}, keywords = {{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}}, doi = {{10.1016/0361-9230(80)90037-4}}, volume = {{5}}, year = {{1980}}, }