PMID- 32150806
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 10
IP  - 3
DP  - 2020 Mar 5
TI  - Flumazenil-Insensitive Benzodiazepine Effects in Recombinant alphabeta and Neuronal 
      GABA(A) Receptors.
LID - 10.3390/brainsci10030150 [doi]
LID - 150
AB  - Gamma-aminobutyric acid, type A (GABA(A)) receptors are complex heterogeneous 
      pentamers with various drug binding sites. Several lines of evidence suggest that 
      benzodiazepines modulate certain GABA(A) receptors in a flumazenil-insensitive 
      manner, possibly via binding sites other than the classical ones. However, 
      GABA(A) receptor subtypes that contain non-classical benzodiazepine binding sites 
      are not systemically studied. The present study investigated the 
      high-concentration effects of three benzodiazepines and their sensitivity to 
      flumazenil on different recombinant (alpha1beta2, alpha2beta2, alpha3beta2, alpha4beta2, alpha5beta2 and alpha1beta3) and 
      native neuronal GABA(A) receptors using the whole-cell patch-clamp 
      electrophysiology technique. The classical benzodiazepine diazepam (200 mumol/L) 
      and midazolam (200 mumol/L) produced flumazenil-insensitive effects on alpha1beta2 
      receptor, whereas the imidazopyridine zolpidem failed to modulate the receptor. 
      Flumazenil-insensitive effects of diazepam were also observed on the alpha2beta2, alpha3beta2 
      and alpha5beta2, but not alpha4beta2 receptors. Unlike beta2-containing receptors, the alpha1beta3 
      receptor was insensitive to diazepam. Moreover, the diazepam (200 mumol/L) effects 
      on some cortical neurons could not be fully antagonized by flumazenil (200 
      mumol/L). These findings suggested that the non-classical (flumazenil-insensitive) 
      benzodiazepine effects depended on certain receptor subtypes and benzodiazepine 
      structures and may be important for designing of subtype- or binding site- 
      specific drugs.
FAU - Lian, Jing-Jing
AU  - Lian JJ
AD  - State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key 
      Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and 
      Toxicology, 27th Taiping Road, Beijing 100850, China.
FAU - Cao, Yan-Qing
AU  - Cao YQ
AD  - State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key 
      Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and 
      Toxicology, 27th Taiping Road, Beijing 100850, China.
FAU - Li, Yu-Lei
AU  - Li YL
AD  - State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key 
      Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and 
      Toxicology, 27th Taiping Road, Beijing 100850, China.
FAU - Yu, Gang
AU  - Yu G
AD  - State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key 
      Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and 
      Toxicology, 27th Taiping Road, Beijing 100850, China.
FAU - Su, Rui-Bin
AU  - Su RB
AD  - State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key 
      Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and 
      Toxicology, 27th Taiping Road, Beijing 100850, China.
LA  - eng
PT  - Journal Article
DEP - 20200305
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC7139822
OTO - NOTNLM
OT  - GABAA receptors
OT  - benzodiazepine
OT  - benzodiazepine binding sites
OT  - diazepam
OT  - alphabeta receptors
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/03/11 06:00
MHDA- 2020/03/11 06:01
PMCR- 2020/03/01
CRDT- 2020/03/11 06:00
PHST- 2020/02/10 00:00 [received]
PHST- 2020/02/28 00:00 [revised]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/03/11 06:00 [entrez]
PHST- 2020/03/11 06:00 [pubmed]
PHST- 2020/03/11 06:01 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - brainsci10030150 [pii]
AID - brainsci-10-00150 [pii]
AID - 10.3390/brainsci10030150 [doi]
PST - epublish
SO  - Brain Sci. 2020 Mar 5;10(3):150. doi: 10.3390/brainsci10030150.