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Br J Pharmacol
2004 Feb 01;1414:717-27. doi: 10.1038/sj.bjp.0705657.
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Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABA rho 1 receptor.
Goutman JD
,
Calvo DJ
.
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1. The mechanisms of action of antagonists of the gamma-aminobutyric acid C (GABA(C)) receptor picrotoxin, quercetin and pregnanolone were studied. 2. Ionic currents (chloride), mediated through human homomeric GABA rho(1) receptors expressed in Xenopus oocytes, were recorded by two-electrode voltage clamp. 3. Dose-response (D-R) curves and kinetic measurements of GABA rho(1) currents were carried out in the presence or absence of antagonists. Use-dependent actions were also evaluated. 4. Picrotoxin, quercetin and pregnanolone exerted noncompetitive actions. 5. IC(50) values measured at the EC(50) for GABA (1 microM) were as follows: picrotoxin 0.6+/-0.1 microM (Hill coefficient n=1.0+/-0.2); quercetin 4.4+/-0.4 microM (n=1.5+/-0.2); pregnanolone 2.1+/-0.5 microM (n=0.8+/-0.1). 6. These antagonists produced changes only in the slope of the linear current-voltage relationships, which was indicative of voltage-independent effects. 7. The effect of picrotoxin on GABA rho(1) currents was use-dependent, strongly relied on agonist concentration and showed a slow onset and offset. The mechanism was compatible with an allosteric inhibition and receptor activation was a prerequisite for antagonism. 8. The effect of quercetin was use-independent, showed relatively fast onset and offset, and resulted in a slowed time course of the GABA-evoked currents. 9. The effect of pregnanolone was use-independent, presented fast onset and a very slow washout, and did not affect current activation. 10. All the antagonists accelerated the time course of deactivation of the GABA rho(1) currents.
Amin,
Homomeric rho 1 GABA channels: activation properties and domains.
1994,
Pubmed
,
Xenbase
Barnard,
International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function.
1998,
Pubmed
Bianchi,
Agonist Trapping by GABAA Receptor Channels.
2001,
Pubmed
Bormann,
GABAC receptors.
1995,
Pubmed
Bowery,
International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function.
2002,
Pubmed
Chang,
Substitutions of the highly conserved M2 leucine create spontaneously opening rho1 gamma-aminobutyric acid receptors.
1998,
Pubmed
,
Xenbase
Chang,
Channel opening locks agonist onto the GABAC receptor.
1999,
Pubmed
Chang,
Site-specific fluorescence reveals distinct structural changes with GABA receptor activation and antagonism.
2002,
Pubmed
,
Xenbase
Chebib,
The 'ABC' of GABA receptors: a brief review.
1999,
Pubmed
Chen,
Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism.
1997,
Pubmed
Cherubini,
Generating diversity at GABAergic synapses.
2001,
Pubmed
Cutting,
Cloning of the gamma-aminobutyric acid (GABA) rho 1 cDNA: a GABA receptor subunit highly expressed in the retina.
1991,
Pubmed
,
Xenbase
Dong,
Use-dependent and use-independent blocking actions of picrotoxin and zinc at the GABAC receptor in retinal horizontal cells.
1996,
Pubmed
Dong,
Zinc downmodulates thf GABAc receptor current in cone horizontal cells acutely isolated from the catfish retina.
1995,
Pubmed
Dong,
Temporal contrast enhancement via GABAC feedback at bipolar terminals in the tiger salamander retina.
1998,
Pubmed
Enz,
Molecular composition of GABAC receptors.
1998,
Pubmed
,
Xenbase
Enz,
Expression of GABA receptor rho 1 and rho 2 subunits in the retina and brain of the rat.
1995,
Pubmed
Feigenspan,
Pharmacology of GABA receptor Cl- channels in rat retinal bipolar cells.
1993,
Pubmed
Feigenspan,
Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells.
1994,
Pubmed
Goutman,
Flavonoid modulation of ionic currents mediated by GABA(A) and GABA(C) receptors.
2003,
Pubmed
,
Xenbase
Gurley,
Point mutations in the M2 region of the alpha, beta, or gamma subunit of the GABAA channel that abolish block by picrotoxin.
1995,
Pubmed
,
Xenbase
Harrison,
Structure-activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex.
1987,
Pubmed
Johnston,
GABAc receptors: relatively simple transmitter -gated ion channels?
1996,
Pubmed
Kusama,
GABA rho 2 receptor pharmacological profile: GABA recognition site similarities to rho 1.
1993,
Pubmed
,
Xenbase
Macdonald,
GABAA receptor channels.
1994,
Pubmed
Majewska,
Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance.
1992,
Pubmed
McCall,
Elimination of the rho1 subunit abolishes GABA(C) receptor expression and alters visual processing in the mouse retina.
2002,
Pubmed
McKernan,
Which GABAA-receptor subtypes really occur in the brain?
1996,
Pubmed
Morris,
Differential modulation of the gamma-aminobutyric acid type C receptor by neuroactive steroids.
1999,
Pubmed
,
Xenbase
Moss,
Constructing inhibitory synapses.
2001,
Pubmed
Newland,
On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat.
1992,
Pubmed
Ogurusu,
Localization of gamma-aminobutyric acid (GABA) receptor rho 3 subunit in rat retina.
1997,
Pubmed
Ogurusu,
Localization of GABA receptor rho 2 and rho 3 subunits in rat brain and functional expression of homooligomeric rho 3 receptors and heterooligomeric rho 2 rho 3 receptors.
1999,
Pubmed
,
Xenbase
Pan,
Agonist-induced closure of constitutively open gamma-aminobutyric acid channels with mutated M2 domains.
1997,
Pubmed
,
Xenbase
Polenzani,
Expression of mammalian gamma-aminobutyric acid receptors with distinct pharmacology in Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Prince,
5 beta-pregnan-3 beta-ol-20-one, a specific antagonist at the neurosteroid site of the GABAA receptor-complex.
1992,
Pubmed
Qian,
Pharmacology of novel GABA receptors found on rod horizontal cells of the white perch retina.
1994,
Pubmed
Ragozzino,
Design and in vitro pharmacology of a selective gamma-aminobutyric acidC receptor antagonist.
1996,
Pubmed
,
Xenbase
Schmidt,
Disinhibition in rat superior colliculus mediated by GABAc receptors.
2001,
Pubmed
Shen,
Multireceptor GABAergic regulation of synaptic communication in amphibian retina.
2001,
Pubmed
Shimada,
gamma-Aminobutyric acid A or C receptor? gamma-Aminobutyric acid rho 1 receptor RNA induces bicuculline-, barbiturate-, and benzodiazepine-insensitive gamma-aminobutyric acid responses in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Sivilotti,
GABA receptor mechanisms in the central nervous system.
1991,
Pubmed
Smart,
Studies on the mechanism of action of picrotoxinin and other convulsants at the crustacean muscle GABA receptor.
1986,
Pubmed
Takahashi,
GABA-induced chloride current in catfish horizontal cells mediated by non-GABAA receptor channels.
1995,
Pubmed
Wang,
A novel gamma-aminobutyric acid receptor subunit (rho 2) cloned from human retina forms bicuculline-insensitive homooligomeric receptors in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Wang,
A single amino acid in gamma-aminobutyric acid rho 1 receptors affects competitive and noncompetitive components of picrotoxin inhibition.
1995,
Pubmed
,
Xenbase
Woodward,
Characterization of bicuculline/baclofen-insensitive gamma-aminobutyric acid receptors expressed in Xenopus oocytes. I. Effects of Cl- channel inhibitors.
1992,
Pubmed
,
Xenbase
Woodward,
Effects of steroids on gamma-aminobutyric acid receptors expressed in Xenopus oocytes by poly(A)+ RNA from mammalian brain and retina.
1992,
Pubmed
,
Xenbase
Woodward,
Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists.
1993,
Pubmed
,
Xenbase
Wotring,
Permeability and single channel conductance of human homomeric rho1 GABAC receptors.
1999,
Pubmed
,
Xenbase
Xu,
Interaction of picrotoxin with GABAA receptor channel-lining residues probed in cysteine mutants.
1995,
Pubmed
,
Xenbase
Yoon,
Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons.
1993,
Pubmed
Zhang,
Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with a methionine residue critical for picrotoxinin channel block.
1995,
Pubmed
,
Xenbase
Zhang,
Structure and function of GABA(C) receptors: a comparison of native versus recombinant receptors.
2001,
Pubmed
