Barbiturate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picrotoxinin/TBPS recognition site

Rosario R. Trifiletti; Adele M. Snowman; Solomon H. Snyder

doi:10.1016/0014-2999(84)90737-4

Barbiturate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picrotoxinin/TBPS recognition site

Rosario R. Trifiletti, Adele M. Snowman, Solomon H. Snyder

School of Medicine

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

The cage convulsant [³⁵S]tert-butylbicyclophosphorothionate ([³⁵S]TBPS) labels a presumed sedative-convulsant receptor complex. The relative potencies of barbiturates in competing for [³⁵S]TBPS binding parallels their potencies in enhancing benzodiazepine receptor binding. Barbiturates inhibit [³⁵S]TBPS binding in a complex, mixed competitive fashion, leading to a decrease in both the apparent affinity of TBPS for its sites and the apparent number of TBPS sites. All of the barbiturates examined markedly accelerate the dissociation of [³⁵S]TBPS from its recognition sites, while picrotoxinin does not affect the dissociation. These results suggest that the barbiturate and picrotoxinin/TBPS recognition sites are distinct but allosterically linked.

Original language	English (US)
Pages (from-to)	441-447
Number of pages	7
Journal	European Journal of Pharmacology
Volume	106
Issue number	2
DOIs	https://doi.org/10.1016/0014-2999(84)90737-4
State	Published - Nov 13 1984

Keywords

Barbiturate
Benzodiazepine
Convulsant
Picrotoxin
Sedative

ASJC Scopus subject areas

Pharmacology

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10.1016/0014-2999(84)90737-4

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title = "Barbiturate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picrotoxinin/TBPS recognition site",

abstract = "The cage convulsant [35S]tert-butylbicyclophosphorothionate ([35S]TBPS) labels a presumed sedative-convulsant receptor complex. The relative potencies of barbiturates in competing for [35S]TBPS binding parallels their potencies in enhancing benzodiazepine receptor binding. Barbiturates inhibit [35S]TBPS binding in a complex, mixed competitive fashion, leading to a decrease in both the apparent affinity of TBPS for its sites and the apparent number of TBPS sites. All of the barbiturates examined markedly accelerate the dissociation of [35S]TBPS from its recognition sites, while picrotoxinin does not affect the dissociation. These results suggest that the barbiturate and picrotoxinin/TBPS recognition sites are distinct but allosterically linked.",

keywords = "Barbiturate, Benzodiazepine, Convulsant, Picrotoxin, Sedative",

author = "Trifiletti, {Rosario R.} and Snowman, {Adele M.} and Snyder, {Solomon H.}",

note = "Funding Information: We thank Dawn C. Dodson and Anita M. Hill for secretarial assistance. Supported by USPHS grants DA-00266, MH-18501, NS-16375, RSA Award DA-00074 to S.H.S., N.I.H. training grant GM-07309 to R.R.T. and a grant of the Mc-Knight Foundation.",

year = "1984",

month = nov,

day = "13",

doi = "10.1016/0014-2999(84)90737-4",

language = "English (US)",

volume = "106",

pages = "441--447",

journal = "European Journal of Pharmacology",

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T1 - Barbiturate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picrotoxinin/TBPS recognition site

AU - Trifiletti, Rosario R.

AU - Snowman, Adele M.

AU - Snyder, Solomon H.

N1 - Funding Information: We thank Dawn C. Dodson and Anita M. Hill for secretarial assistance. Supported by USPHS grants DA-00266, MH-18501, NS-16375, RSA Award DA-00074 to S.H.S., N.I.H. training grant GM-07309 to R.R.T. and a grant of the Mc-Knight Foundation.

PY - 1984/11/13

Y1 - 1984/11/13

N2 - The cage convulsant [35S]tert-butylbicyclophosphorothionate ([35S]TBPS) labels a presumed sedative-convulsant receptor complex. The relative potencies of barbiturates in competing for [35S]TBPS binding parallels their potencies in enhancing benzodiazepine receptor binding. Barbiturates inhibit [35S]TBPS binding in a complex, mixed competitive fashion, leading to a decrease in both the apparent affinity of TBPS for its sites and the apparent number of TBPS sites. All of the barbiturates examined markedly accelerate the dissociation of [35S]TBPS from its recognition sites, while picrotoxinin does not affect the dissociation. These results suggest that the barbiturate and picrotoxinin/TBPS recognition sites are distinct but allosterically linked.

AB - The cage convulsant [35S]tert-butylbicyclophosphorothionate ([35S]TBPS) labels a presumed sedative-convulsant receptor complex. The relative potencies of barbiturates in competing for [35S]TBPS binding parallels their potencies in enhancing benzodiazepine receptor binding. Barbiturates inhibit [35S]TBPS binding in a complex, mixed competitive fashion, leading to a decrease in both the apparent affinity of TBPS for its sites and the apparent number of TBPS sites. All of the barbiturates examined markedly accelerate the dissociation of [35S]TBPS from its recognition sites, while picrotoxinin does not affect the dissociation. These results suggest that the barbiturate and picrotoxinin/TBPS recognition sites are distinct but allosterically linked.

KW - Barbiturate

KW - Benzodiazepine

KW - Convulsant

KW - Picrotoxin

KW - Sedative

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Barbiturate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picrotoxinin/TBPS recognition site

Abstract

Keywords

ASJC Scopus subject areas

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