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Molecular basis for the different binding properties of benzodiazepines to human and bovine peripheral-type benzodiazepine receptors

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
335
Issue
3
Identifiers
DOI: 10.1016/0014-5793(93)80407-l
Keywords
  • Chimaeric
  • Mitochondrial Receptor
  • Recombinant Yeast
  • Pk11195
  • Ro5-4864

Abstract

Abstract The 18 kDa peripheral benzodiazepine receptor (PBR) can be labelled by benzodiazepines, such as Ro5-4864, and isoquinoline carboxamides such as PK11195. These two compounds are reversible competitive inhibitors of each other. However, while the binding affinity of Ro5-4864 varies enormously across species, PK11195 always displays high affinity, suggesting that their binding domains are overlapping but not identical. We report here that recombinant human and bovine PBR produced in yeast, a microorganism devoid of endogenous PBR, can be labelled with [ 3H]PK11195, but only the human receptor can be labelled with [ 3H]Ro5-4864. Furthermore, we identified, through the binding analysis of human-bovine chimaeric receptors, a region near the C-terminal end of the PBR, with only five non-conserved amino acids between human and bovine sequences, as responsible for the difference in high affinity binding of Ro5-4864 to the two receptors.

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