T. Yakushiji et al., DIFFERENTIAL PROPERTIES OF TYPE-I AND TYPE-II BENZODIAZEPINE RECEPTORS IN MAMMALIAN CNS NEURONS, British Journal of Pharmacology, 109(3), 1993, pp. 819-825
1 The effects of benzodiazepine receptor (BZR) partial agonists, Y-236
84 and CL218,872, were compared with its full agonist, diazepam, on ga
mma-aminobutyric acid (GABA)-induced Cl- current (I(Cl)) in acutely di
ssociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spi
nal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp te
chnique. 2 The GABA-induced responses were essentially the same in bot
h 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 Enhanc
ement of the GABA response by the two partial agonists was about one-t
hird of that by diazepam in the SVH neurones (where type II subtype of
BZR, BZ2, is predominant), whereas these partial agonists potentiated
the GABA response as much as diazepam in CPJ neurones (where the type
I subtype of BZR, BZ1, is predominant). In CTX neurones where both ty
pe 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. Al
so, in all preparations, the threshold concentration and K(D) values o
f diazepam action were 10 fold less than those induced by partial agon
ists. 5 All BZR agonists shifted the concentration-response relationsh
ip for GABA to the left without changing the maximum current amplitude
, indicating that activation of both BZ1 and BZ2 increase the affinity
of the GABA(A) receptor for GABA. 6 The results are important in clar
ifying the mechanism of anxiety and might explain the anxioselectivity
of BZR partial agonists.