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Labelling of “Peripheral‐Type” Benzodiazepine Binding Sites in the Rat Brain By Using [ 3 H]PK 11195, an Isoquinoline Carboxamide Derivative: Kinetic Studies and Autoradiographic Localization
Author(s) -
Benavides J.,
Quarteronet D.,
Imbault F.,
Malgouris C.,
Uzan A.,
Renault C.,
Dubroeucq M. C.,
Gueremy C.,
Fur G. Le
Publication year - 1983
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1983.tb00888.x
Subject(s) - isoquinoline , derivative (finance) , labelling , peripheral , chemistry , benzodiazepine , carboxamide , stereochemistry , nuclear magnetic resonance , biochemistry , medicine , physics , receptor , financial economics , economics
PK 11195 [1‐(2‐chlorophenyl)‐ N ‐methyl‐ N ‐(1‐methylpropyl)‐3‐isoquinolinecarboxamide] is a new ligand for the “peripheral‐type” benzodiazepine binding sites, chemically unrelated to benzodiazepines. It displaces with a very high potency (IC 50 × 10 −9 M ) [ 3 H]‐RO5–4864 (a benzodiazepine which specifically labels the peripheral‐type sites) from its binding sites. [ 3 H]PK 11195 binds to a membrane fraction from rat brain cortex and rat olfactory bulb in a saturable and reversible manner with a very high affinity (K D = 10 −9 M ). The number of maximal binding sites was ten times greater in the olfactory bulb than in the brain cortex. The order of potency of several compounds as displacers at 25°C (PK 11195 > RO5–4864 > diazepam > dipyridamole > clonazepam) demonstrates that [ 3 H]PK 11195 binds to the peripheral‐type benzodiazepine binding sites. The K D value for the [ 3 H]PK 11195 binding is not affected by temperature changes, whereas RO5–4864 and diazepam affinities decrease with increasing temperatures. Autoradiographic images of [ 3 H]PK 11195 binding to rat brain sections show that binding sites are mainly localized in the olfactory bulb, median eminence, choroid plexus, and ependyma. This ligand could be a useful tool to elucidate the physiological and pharmacological relevance of these binding sites.