Pharmacology of recombinant γ-aminobutyric acida receptors rendered diazepam-insensitive by point-mutated α-subunits

Jack A. Benson, Karin Löw, Ruth Keist, Hanns Mohler, Uwe Rudolph

Research output: Contribution to journalArticlepeer-review

Abstract

Amino acids in the α- and γ-subunits contribute to the benzodiazepine binding site of GABA(A)-receptors. We show that the mutation of a conserved histidine residue in the N-terminal extracellular segment (α1(H101R), α2(H101R), α3(H126R), and α5(H1015R) results not only in diazepam-insensitivity of the respective αxβ2,γ2-receptors but also in an increased potentiation of the GABA-induced currents by the partial agonist bretazenil. Furthermore, Ro 15-4513, an inverse agonist at wild-type receptors, acts as an agonist at all mutant receptors. This conserved molecular switch can be exploited to identify the pharmacological significance of specific GABA(A)-receptor subtypes in vivo.

Original languageEnglish (US)
Pages (from-to)400-404
Number of pages5
JournalFEBS Letters
Volume431
Issue number3
DOIs
StatePublished - Jul 24 1998
Externally publishedYes

Keywords

  • Benzodiazepine
  • Central nervous system
  • Neurotransmitter
  • Receptor
  • Recombinant
  • γ-Aminobutyric acid

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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