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Evidence for inhibitory effect of the agonist gaboxadol at human alpha(1)beta(2)gamma S-2 GABA(A) receptors

Smith, Morten LU ; Lindquist, Catarina LU and Birnir, Bryndis LU (2003) In European Journal of Pharmacology 478(1). p.21-26
Abstract
Gaboxadol (THIP; 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is an agonist at GABA(A) receptors. THIP concentrations (0.01-50 mM) were applied rapidly to Sf9 cells expressing the human alpha(1)beta(2)gamma(2S) GABA(A) receptors. The EC50 values for the peak current in THIP alone or THIP plus 1 muM diazepam were 154 and 53 muM, respectively. In supersaturating THIP (10-50 mM) the rate of current decay increased and an off-current developed when THIP was rapidly removed. The mean currents measured over the first 4 s in 10 mM and higher THIP concentrations were 0.6 or less of the 1 mM THIP mean current. Diazepam (1 muM) increased the 4 s mean current when evoked by 10 to 20 mM THIP but not 50 mM THIP. No similar effects on the current... (More)
Gaboxadol (THIP; 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is an agonist at GABA(A) receptors. THIP concentrations (0.01-50 mM) were applied rapidly to Sf9 cells expressing the human alpha(1)beta(2)gamma(2S) GABA(A) receptors. The EC50 values for the peak current in THIP alone or THIP plus 1 muM diazepam were 154 and 53 muM, respectively. In supersaturating THIP (10-50 mM) the rate of current decay increased and an off-current developed when THIP was rapidly removed. The mean currents measured over the first 4 s in 10 mM and higher THIP concentrations were 0.6 or less of the 1 mM THIP mean current. Diazepam (1 muM) increased the 4 s mean current when evoked by 10 to 20 mM THIP but not 50 mM THIP. No similar effects on the current time-course were recorded in supersaturating gamma-aminobutyric acid (GABA) concentrations (50 and 80 mM). The results demonstrate an inhibitory as well as agonist effect of THIP at alpha(1)beta(2)gamma(2s) GABA(A) receptors. (C) 2003 Elsevier B.V. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
7-tetrahydroisoxazolo[5, 6, 5, 4-c]pyridin-3-ol), THIP (4, gamma-aminobutyric acid, benzodiazepine, litmnd-gated, anaesthetic, inhibition
in
European Journal of Pharmacology
volume
478
issue
1
pages
21 - 26
publisher
Elsevier
external identifiers
  • pmid:14555180
  • wos:000185993700003
  • scopus:1642289929
ISSN
1879-0712
DOI
language
English
LU publication?
yes
id
eef95242-7554-48e9-82b4-5c5e77087fd6 (old id 298447)
date added to LUP
2007-09-22 11:06:37
date last changed
2018-05-29 11:38:53
@article{eef95242-7554-48e9-82b4-5c5e77087fd6,
  abstract     = {Gaboxadol (THIP; 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is an agonist at GABA(A) receptors. THIP concentrations (0.01-50 mM) were applied rapidly to Sf9 cells expressing the human alpha(1)beta(2)gamma(2S) GABA(A) receptors. The EC50 values for the peak current in THIP alone or THIP plus 1 muM diazepam were 154 and 53 muM, respectively. In supersaturating THIP (10-50 mM) the rate of current decay increased and an off-current developed when THIP was rapidly removed. The mean currents measured over the first 4 s in 10 mM and higher THIP concentrations were 0.6 or less of the 1 mM THIP mean current. Diazepam (1 muM) increased the 4 s mean current when evoked by 10 to 20 mM THIP but not 50 mM THIP. No similar effects on the current time-course were recorded in supersaturating gamma-aminobutyric acid (GABA) concentrations (50 and 80 mM). The results demonstrate an inhibitory as well as agonist effect of THIP at alpha(1)beta(2)gamma(2s) GABA(A) receptors. (C) 2003 Elsevier B.V. All rights reserved.},
  author       = {Smith, Morten and Lindquist, Catarina and Birnir, Bryndis},
  issn         = {1879-0712},
  keyword      = {7-tetrahydroisoxazolo[5,6,5,4-c]pyridin-3-ol),THIP (4,gamma-aminobutyric acid,benzodiazepine,litmnd-gated,anaesthetic,inhibition},
  language     = {eng},
  number       = {1},
  pages        = {21--26},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Evidence for inhibitory effect of the agonist gaboxadol at human alpha(1)beta(2)gamma S-2 GABA(A) receptors},
  url          = {http://dx.doi.org/},
  volume       = {478},
  year         = {2003},
}