Use of ligands with low nanomolar affinity for the GABAB receptor: Effect of CGP 55845A on the release of amino acids

J. Kardos, T. Blandl, I. Kovács, K. A. Kékesi, A. Reichart, G. Nyitrai, Á Dobolyi, G. Juhász

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

To assess antagonistic properties of the nanomolar affinity GABAB receptor ligand, CGP 55845A (IC50 = 1.1 ± 0.2 nM), 3H-D-Aspartate release from synaptosomes at 22-24°C was measured in combination with the use of a fast perfusion technique, in vitro. The inhibition of high K+ elicited 3H-D-aspartate release by 250 μM (R)-baclofen was blocked by 10 μM CGP 55845A. The concomitant two-fold increase of basal aspartate release was comparable to that of freely moving rats as measured by a HPLC combined microdialysis technique, in vivo. A low concentration of CGP 55845A (250 nM) induced two release-pulses of glutamate whereas much less or no release (or release inhibition) was detected with aspartate, serine, glycine and glutamine. By contrast, one order of magnitude higher dose of CGP 55845A induced similar, double-release patterns of neurotransmitters and serine, however the relative amounts of released glutamate (15-fold) and aspartate (55-fold) were reversed in the second pulse.

Original languageEnglish
Pages (from-to)153-157
Number of pages5
JournalPharmacology Reviews and Communications
Volume8
Issue number2-3
Publication statusPublished - 1996

Fingerprint

CGP 55845A
Aspartic Acid
Ligands
D-Aspartic Acid
Amino Acids
Serine
Glutamic Acid
Baclofen
Synaptosomes
Microdialysis
Glutamine
Glycine
Inhibitory Concentration 50
Neurotransmitter Agents
Perfusion
High Pressure Liquid Chromatography

Keywords

  • H-D-Aspartate release
  • H-R-Baclofen binding
  • Amino acids
  • Freely moving rat
  • Microdialysis
  • Synaptosomal fraction

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Use of ligands with low nanomolar affinity for the GABAB receptor: Effect of CGP 55845A on the release of amino acids",
abstract = "To assess antagonistic properties of the nanomolar affinity GABAB receptor ligand, CGP 55845A (IC50 = 1.1 ± 0.2 nM), 3H-D-Aspartate release from synaptosomes at 22-24°C was measured in combination with the use of a fast perfusion technique, in vitro. The inhibition of high K+ elicited 3H-D-aspartate release by 250 μM (R)-baclofen was blocked by 10 μM CGP 55845A. The concomitant two-fold increase of basal aspartate release was comparable to that of freely moving rats as measured by a HPLC combined microdialysis technique, in vivo. A low concentration of CGP 55845A (250 nM) induced two release-pulses of glutamate whereas much less or no release (or release inhibition) was detected with aspartate, serine, glycine and glutamine. By contrast, one order of magnitude higher dose of CGP 55845A induced similar, double-release patterns of neurotransmitters and serine, however the relative amounts of released glutamate (15-fold) and aspartate (55-fold) were reversed in the second pulse.",
keywords = "H-D-Aspartate release, H-R-Baclofen binding, Amino acids, Freely moving rat, Microdialysis, Synaptosomal fraction",
author = "J. Kardos and T. Blandl and I. Kov{\'a}cs and K{\'e}kesi, {K. A.} and A. Reichart and G. Nyitrai and {\'A} Dobolyi and G. Juh{\'a}sz",
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T1 - Use of ligands with low nanomolar affinity for the GABAB receptor

T2 - Effect of CGP 55845A on the release of amino acids

AU - Kardos, J.

AU - Blandl, T.

AU - Kovács, I.

AU - Kékesi, K. A.

AU - Reichart, A.

AU - Nyitrai, G.

AU - Dobolyi, Á

AU - Juhász, G.

PY - 1996

Y1 - 1996

N2 - To assess antagonistic properties of the nanomolar affinity GABAB receptor ligand, CGP 55845A (IC50 = 1.1 ± 0.2 nM), 3H-D-Aspartate release from synaptosomes at 22-24°C was measured in combination with the use of a fast perfusion technique, in vitro. The inhibition of high K+ elicited 3H-D-aspartate release by 250 μM (R)-baclofen was blocked by 10 μM CGP 55845A. The concomitant two-fold increase of basal aspartate release was comparable to that of freely moving rats as measured by a HPLC combined microdialysis technique, in vivo. A low concentration of CGP 55845A (250 nM) induced two release-pulses of glutamate whereas much less or no release (or release inhibition) was detected with aspartate, serine, glycine and glutamine. By contrast, one order of magnitude higher dose of CGP 55845A induced similar, double-release patterns of neurotransmitters and serine, however the relative amounts of released glutamate (15-fold) and aspartate (55-fold) were reversed in the second pulse.

AB - To assess antagonistic properties of the nanomolar affinity GABAB receptor ligand, CGP 55845A (IC50 = 1.1 ± 0.2 nM), 3H-D-Aspartate release from synaptosomes at 22-24°C was measured in combination with the use of a fast perfusion technique, in vitro. The inhibition of high K+ elicited 3H-D-aspartate release by 250 μM (R)-baclofen was blocked by 10 μM CGP 55845A. The concomitant two-fold increase of basal aspartate release was comparable to that of freely moving rats as measured by a HPLC combined microdialysis technique, in vivo. A low concentration of CGP 55845A (250 nM) induced two release-pulses of glutamate whereas much less or no release (or release inhibition) was detected with aspartate, serine, glycine and glutamine. By contrast, one order of magnitude higher dose of CGP 55845A induced similar, double-release patterns of neurotransmitters and serine, however the relative amounts of released glutamate (15-fold) and aspartate (55-fold) were reversed in the second pulse.

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KW - Freely moving rat

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KW - Synaptosomal fraction

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