Alkyl-substituted γ-butyrolactones act at a distinct site allosterically linked to the TBPS/picrotoxinin site on the GABAA receptor complex

Katherine D. Holland; Michael G. Bouley; Douglas F. Covey; James A. Ferrendelli

doi:10.1016/0006-8993(93)91128-F

Alkyl-substituted γ-butyrolactones act at a distinct site allosterically linked to the TBPS/picrotoxinin site on the GABA_A receptor complex

Katherine D. Holland
, Michael G. Bouley
, Douglas F. Covey
, James A. Ferrendelli

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

23 Scopus citations

Abstract

Effects of alkyl-substituted γ-butyrolactones and γ-thiobutyrolactones on [³⁵S]t-butylbicyclophosphorothionate (³⁵S-TBPS) dissociation from the picrotoxinireceptor were studied. Unlike picrotoxin, these lactones accelerated the dissociation rate of ³⁵S-TBPS. Thus, previous reports that these lactones change the K_d but not the B_max of ³⁵S-TBPS in equilibrium binding experiments is explained not by competitive inhibition, but by an allosteric interaction with the ³⁵S-TBPS binding site. These results indicate that modulatory effects of alkyl-substituted γ-butyrolactones may result from their action at a distinct site on the γ-aminobutyric acid (GABA)_A receptor.

Original language	English
Pages (from-to)	170-174
Number of pages	5
Journal	Brain Research
Volume	615
Issue number	1
DOIs	https://doi.org/10.1016/0006-8993(93)91128-F
State	Published - Jun 25 1993

Keywords

Picrotoxin
[S]t-Butylbicyclophosphorothionate
γ-Aminobutyric acid
γ-Aminobutyric acid receptor
γ-Butyrolactone

Access to Document

10.1016/0006-8993(93)91128-F

Cite this

@article{59e9514dc27f4f07a39b051550633303,

title = "Alkyl-substituted γ-butyrolactones act at a distinct site allosterically linked to the TBPS/picrotoxinin site on the GABAA receptor complex",

abstract = "Effects of alkyl-substituted γ-butyrolactones and γ-thiobutyrolactones on [35S]t-butylbicyclophosphorothionate (35S-TBPS) dissociation from the picrotoxinireceptor were studied. Unlike picrotoxin, these lactones accelerated the dissociation rate of 35S-TBPS. Thus, previous reports that these lactones change the Kd but not the Bmax of 35S-TBPS in equilibrium binding experiments is explained not by competitive inhibition, but by an allosteric interaction with the 35S-TBPS binding site. These results indicate that modulatory effects of alkyl-substituted γ-butyrolactones may result from their action at a distinct site on the γ-aminobutyric acid (GABA)A receptor.",

keywords = "Picrotoxin, [S]t-Butylbicyclophosphorothionate, γ-Aminobutyric acid, γ-Aminobutyric acid receptor, γ-Butyrolactone",

author = "Holland, \{Katherine D.\} and Bouley, \{Michael G.\} and Covey, \{Douglas F.\} and Ferrendelli, \{James A.\}",

year = "1993",

month = jun,

day = "25",

doi = "10.1016/0006-8993(93)91128-F",

language = "English",

volume = "615",

pages = "170--174",

journal = "Brain Research",

issn = "0006-8993",

number = "1",

}

TY - JOUR

T1 - Alkyl-substituted γ-butyrolactones act at a distinct site allosterically linked to the TBPS/picrotoxinin site on the GABAA receptor complex

AU - Holland, Katherine D.

AU - Bouley, Michael G.

AU - Covey, Douglas F.

AU - Ferrendelli, James A.

PY - 1993/6/25

Y1 - 1993/6/25

N2 - Effects of alkyl-substituted γ-butyrolactones and γ-thiobutyrolactones on [35S]t-butylbicyclophosphorothionate (35S-TBPS) dissociation from the picrotoxinireceptor were studied. Unlike picrotoxin, these lactones accelerated the dissociation rate of 35S-TBPS. Thus, previous reports that these lactones change the Kd but not the Bmax of 35S-TBPS in equilibrium binding experiments is explained not by competitive inhibition, but by an allosteric interaction with the 35S-TBPS binding site. These results indicate that modulatory effects of alkyl-substituted γ-butyrolactones may result from their action at a distinct site on the γ-aminobutyric acid (GABA)A receptor.

AB - Effects of alkyl-substituted γ-butyrolactones and γ-thiobutyrolactones on [35S]t-butylbicyclophosphorothionate (35S-TBPS) dissociation from the picrotoxinireceptor were studied. Unlike picrotoxin, these lactones accelerated the dissociation rate of 35S-TBPS. Thus, previous reports that these lactones change the Kd but not the Bmax of 35S-TBPS in equilibrium binding experiments is explained not by competitive inhibition, but by an allosteric interaction with the 35S-TBPS binding site. These results indicate that modulatory effects of alkyl-substituted γ-butyrolactones may result from their action at a distinct site on the γ-aminobutyric acid (GABA)A receptor.

KW - Picrotoxin

KW - [S]t-Butylbicyclophosphorothionate

KW - γ-Aminobutyric acid

KW - γ-Aminobutyric acid receptor

KW - γ-Butyrolactone

UR - https://www.scopus.com/pages/publications/0027256569

U2 - 10.1016/0006-8993(93)91128-F

DO - 10.1016/0006-8993(93)91128-F

M3 - Article

C2 - 8395954

AN - SCOPUS:0027256569

SN - 0006-8993

VL - 615

SP - 170

EP - 174

JO - Brain Research

JF - Brain Research

IS - 1

ER -

Alkyl-substituted γ-butyrolactones act at a distinct site allosterically linked to the TBPS/picrotoxinin site on the GABA_A receptor complex

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this