PMID- 2836561
OWN - NLM
STAT- MEDLINE
DCOM- 19880628
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 50
IP  - 6
DP  - 1988 Jun
TI  - GABAA receptor populations bind agonists and antagonists differentially and with 
      opposite affinities.
PG  - 1865-71
AB  - Pretreatment of synaptosomal membranes with a diazo-coupling reagent and the 
      presence of Cl- ions were used to differentiate high- and low-affinity 
      populations of postsynaptic gamma-aminobutyric acid (GABAA) receptors. The 
      super-low-affinity GABAA receptors were characterized by the enhancing effect of 
      GABA on [3H]diazepam binding. The GABA antagonists 
      2-(3-carboxypropyl)-3-amino-4-methyl-6-phenylpyridazinium chloride (SR 95103) and 
      3-alpha-hydroxy-16-imino-5 beta-17-aza-androstan-11-one (R 5135) shifted and 
      suppressed the dose-response curve of GABA on diazepam binding. SR 95103 
      displaced the lower affinity [3H]GABA binding with higher potency. Dissociation 
      of the binding of the antagonist 
      2-(3-carboxypropyl)-3-amino-6-p-methoxyphenylpyridazinium bromide ([3H]SR 95531) 
      was polyphasic. Displacing potencies of SR 95531 and GABA were examined on the 
      major (85%) rapid and minor slower phases of dissociation separated kinetically. 
      The slower phase corresponded to higher affinity binding of SR 95531 which was 
      displaced by GABA with about 10 times less potency. Photoaffinity labeling with 
      muscimol decreased the number of [3H]muscimol binding sites by 27%. It decreased 
      the displacing potency of GABA by 72%, but not that of bicuculline methiodide. 
      These findings can be explained by a preferential binding of antagonists to 
      hydrophobic accessory sites around low-affinity GABAA receptors.
FAU - Maksay, G
AU  - Maksay G
AD  - Laboratory of Pharmacodynamics, Hungarian Academy of Sciences, Budapest.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Affinity Labels)
RN  - 0 (Androstanes)
RN  - 0 (Azasteroids)
RN  - 0 (Diazonium Compounds)
RN  - 0 (GABA Antagonists)
RN  - 0 (Pyridazines)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Sulfanilic Acids)
RN  - 2763-96-4 (Muscimol)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 96440-63-0 (2-(carboxy-3'-propyl)-3-amino-4-methyl-6-phenylpyridazinium chloride)
RN  - 99460MG420 (gabazine)
RN  - Q3JTX2Q7TU (Diazepam)
RN  - R1OGA081AP (RU 5135)
RN  - Z0105S98AO (diazobenzenesulfonic acid)
SB  - IM
MH  - Affinity Labels
MH  - Androstanes/metabolism
MH  - Animals
MH  - Azasteroids/metabolism
MH  - Brain/*metabolism
MH  - Diazepam/*metabolism
MH  - Diazonium Compounds/pharmacology
MH  - *GABA Antagonists
MH  - Male
MH  - Muscimol/metabolism
MH  - Photochemistry
MH  - Pyridazines/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, GABA-A/drug effects/*metabolism
MH  - Sulfanilic Acids/pharmacology
MH  - Synaptic Membranes/*metabolism
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 1988/06/01 00:00
MHDA- 1988/06/01 00:01
CRDT- 1988/06/01 00:00
PHST- 1988/06/01 00:00 [pubmed]
PHST- 1988/06/01 00:01 [medline]
PHST- 1988/06/01 00:00 [entrez]
AID - 10.1111/j.1471-4159.1988.tb02490.x [doi]
PST - ppublish
SO  - J Neurochem. 1988 Jun;50(6):1865-71. doi: 10.1111/j.1471-4159.1988.tb02490.x.