Inhibition of [3H]GABA binding to rat brain synaptic membranes by bicuculline related alkaloids

J. Kardos, Gábor Blaskó, Péter Kerekes, Ilona Kovács, M. Simonyi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The binding of 45 bicuculline related phthalideisoquinoline alkaloids to the GABAA receptor was studied using rat brain synaptic membranes prepared both in Tris-HCl and in Tyrode buffers. The IC50 values determined in Tyrode for phthalideisoquinolines are lower (by about one order of magnitude) than and correlate well (r2 = 0.95) with the IC50 data obtained by [3H]GABA displacement in Tris-HCl. Applying Tyrode, the activities of GABA agonists relative to Tris-HCl are decreased. It can be recognized that activities in receptor binding are dependent on the conformations phthalideisoquinolines prefer in solution. On the basis of systematic alterations in the phthalideisoquinoline molecule the main structural elements involved in the binding of phthalideisoquinoline alkaloids appear to be identical with those of GABA agonists, suggesting that the same binding conformation of the GABAA receptor may be implicated for both agonists and antagonists. The opposite shift in relative potencies of agonists and antagonists may be the consequence of an alteration in the "ionic status" rather than that in the conformation of the GABAA receptor.

Original languageEnglish
Pages (from-to)3537-3545
Number of pages9
JournalBiochemical Pharmacology
Volume33
Issue number22
DOIs
Publication statusPublished - Nov 15 1984

Fingerprint

Synaptic Membranes
Bicuculline
GABA-A Receptors
Alkaloids
gamma-Aminobutyric Acid
GABA Agonists
Conformations
Rats
Brain
Membranes
Inhibitory Concentration 50
Buffers
Molecules

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of [3H]GABA binding to rat brain synaptic membranes by bicuculline related alkaloids. / Kardos, J.; Blaskó, Gábor; Kerekes, Péter; Kovács, Ilona; Simonyi, M.

In: Biochemical Pharmacology, Vol. 33, No. 22, 15.11.1984, p. 3537-3545.

Research output: Contribution to journalArticle

Kardos, J. ; Blaskó, Gábor ; Kerekes, Péter ; Kovács, Ilona ; Simonyi, M. / Inhibition of [3H]GABA binding to rat brain synaptic membranes by bicuculline related alkaloids. In: Biochemical Pharmacology. 1984 ; Vol. 33, No. 22. pp. 3537-3545.
@article{6c9166a749cd45b4b8a69870ccc15c1a,
title = "Inhibition of [3H]GABA binding to rat brain synaptic membranes by bicuculline related alkaloids",
abstract = "The binding of 45 bicuculline related phthalideisoquinoline alkaloids to the GABAA receptor was studied using rat brain synaptic membranes prepared both in Tris-HCl and in Tyrode buffers. The IC50 values determined in Tyrode for phthalideisoquinolines are lower (by about one order of magnitude) than and correlate well (r2 = 0.95) with the IC50 data obtained by [3H]GABA displacement in Tris-HCl. Applying Tyrode, the activities of GABA agonists relative to Tris-HCl are decreased. It can be recognized that activities in receptor binding are dependent on the conformations phthalideisoquinolines prefer in solution. On the basis of systematic alterations in the phthalideisoquinoline molecule the main structural elements involved in the binding of phthalideisoquinoline alkaloids appear to be identical with those of GABA agonists, suggesting that the same binding conformation of the GABAA receptor may be implicated for both agonists and antagonists. The opposite shift in relative potencies of agonists and antagonists may be the consequence of an alteration in the {"}ionic status{"} rather than that in the conformation of the GABAA receptor.",
author = "J. Kardos and G{\'a}bor Blask{\'o} and P{\'e}ter Kerekes and Ilona Kov{\'a}cs and M. Simonyi",
year = "1984",
month = "11",
day = "15",
doi = "10.1016/0006-2952(84)90134-5",
language = "English",
volume = "33",
pages = "3537--3545",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "22",

}

TY - JOUR

T1 - Inhibition of [3H]GABA binding to rat brain synaptic membranes by bicuculline related alkaloids

AU - Kardos, J.

AU - Blaskó, Gábor

AU - Kerekes, Péter

AU - Kovács, Ilona

AU - Simonyi, M.

PY - 1984/11/15

Y1 - 1984/11/15

N2 - The binding of 45 bicuculline related phthalideisoquinoline alkaloids to the GABAA receptor was studied using rat brain synaptic membranes prepared both in Tris-HCl and in Tyrode buffers. The IC50 values determined in Tyrode for phthalideisoquinolines are lower (by about one order of magnitude) than and correlate well (r2 = 0.95) with the IC50 data obtained by [3H]GABA displacement in Tris-HCl. Applying Tyrode, the activities of GABA agonists relative to Tris-HCl are decreased. It can be recognized that activities in receptor binding are dependent on the conformations phthalideisoquinolines prefer in solution. On the basis of systematic alterations in the phthalideisoquinoline molecule the main structural elements involved in the binding of phthalideisoquinoline alkaloids appear to be identical with those of GABA agonists, suggesting that the same binding conformation of the GABAA receptor may be implicated for both agonists and antagonists. The opposite shift in relative potencies of agonists and antagonists may be the consequence of an alteration in the "ionic status" rather than that in the conformation of the GABAA receptor.

AB - The binding of 45 bicuculline related phthalideisoquinoline alkaloids to the GABAA receptor was studied using rat brain synaptic membranes prepared both in Tris-HCl and in Tyrode buffers. The IC50 values determined in Tyrode for phthalideisoquinolines are lower (by about one order of magnitude) than and correlate well (r2 = 0.95) with the IC50 data obtained by [3H]GABA displacement in Tris-HCl. Applying Tyrode, the activities of GABA agonists relative to Tris-HCl are decreased. It can be recognized that activities in receptor binding are dependent on the conformations phthalideisoquinolines prefer in solution. On the basis of systematic alterations in the phthalideisoquinoline molecule the main structural elements involved in the binding of phthalideisoquinoline alkaloids appear to be identical with those of GABA agonists, suggesting that the same binding conformation of the GABAA receptor may be implicated for both agonists and antagonists. The opposite shift in relative potencies of agonists and antagonists may be the consequence of an alteration in the "ionic status" rather than that in the conformation of the GABAA receptor.

UR - http://www.scopus.com/inward/record.url?scp=0021645749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021645749&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(84)90134-5

DO - 10.1016/0006-2952(84)90134-5

M3 - Article

C2 - 6095852

AN - SCOPUS:0021645749

VL - 33

SP - 3537

EP - 3545

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 22

ER -