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Molecular basis for the different binding properties of benzodiazepines to human and bovine peripheral‐type benzodiazepine receptors
Author(s) -
Farges Roseli,
Joseph-Liauzun Evelyne,
Shire David,
Caput Daniel,
Le Fur Gerard,
Loison Gerard,
Ferrara Pascual
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80407-l
Subject(s) - receptor , isoquinoline , recombinant dna , yeast , biochemistry , binding site , endogeny , biology , benzodiazepine , gabaa receptor , chemistry , pharmacology , stereochemistry , gene
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 [ 3 H]PK11195, but only the human receptor can be labelled with [ 3 H]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.