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Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones
Author(s) -
Yakushiji Takashi,
Shirasaki Tetsuya,
Munakata Mitsutoshi,
Hirata Akira,
Akaike Norio
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13648.x
Subject(s) - partial agonist , agonist , diazepam , chemistry , gabaa receptor , benzodiazepine , receptor , medicine , patch clamp , pharmacology , endocrinology , biology , biochemistry
1 The effects of benzodiazepine receptor (BZR) partial agonists, Y‐23684 and CL218,872, were compared with its full agonist, diazepam, on γ‐aminobutyric acid (GABA)‐induced Cl − current ( I Cl ) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole‐cell mode patch‐clamp technique. 2 The GABA‐induced responses were essentially the same in both SVH and CPJ neurones, but the K D value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3 Enhancement of the GABA response by the two partial agonists was about one‐third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ 2 , is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ 1 , is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4 In concentration‐response relationships of BZR partial agonists, the threshold concentrations, K D values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and K D values of diazepam action were 10 fold less than those induced by partial agonists. 5 All BZR agonists shifted the concentration‐response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ 1 and BZ 2 increase the affinity of the GABA A receptor for GABA. 6 The results are important in clarifying the mechanism of anxiety and might explain the anxioselectivity of BZR partial agonists.