PMID- 2831314
OWN - NLM
STAT- MEDLINE
DCOM- 19880414
LR  - 20191101
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 8
IP  - 3
DP  - 1988 Mar
TI  - Modulation of neurotransmitter receptor desensitization: chlordiazepoxide 
      stimulates fading of the GABA response.
PG  - 814-20
AB  - Benzodiazepines are neuromodulatory drugs that potentiate GABA-mediated 
      conductance increases. We report the findings of an investigation into the effect 
      of a full benzodiazepine-positive modulator (agonist), chlordiazepoxide (CDPX), 
      on desensitization of the GABA response in chick spinal cord neurons maintained 
      in primary monolayer cell culture. GABA application initially increases cell 
      conductance, which then desensitizes. CDPX increases the apparent rate constant 
      and extent of desensitization for the GABA response. The observed values for rate 
      constant and extent of desensitization in the presence of CDPX are significantly 
      greater than the values predicted for an equivalent peak response to GABA alone. 
      Flunitrazepam, another full positive modulator, also stimulates the rate constant 
      for GABA-induced desensitization. Furthermore, a weak partial 
      benzodiazepine-positive modulator, Ro 15-1788 (an imidazodiazepine) (1) exhibits 
      little or no potentiation of GABA-induced desensitization, and (2) antagonizes 
      the ability of CDPX to stimulate GABA desensitization. The results demonstrate a 
      novel form of neuromodulator action: the stimulation of receptor desensitization 
      that cannot be explained by channel blockade. Thus, benzodiazepine modulators 
      have the capacity to increase GABA receptor desensitization while increasing the 
      peak response to GABA.
FAU - Mierlak, D
AU  - Mierlak D
AD  - Department of Anatomy and Cell Biology, State University of New York, Health 
      Science Center at Brooklyn 11203.
FAU - Farb, D H
AU  - Farb DH
LA  - eng
GR  - R01-NS22116/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Receptors, GABA-A)
RN  - 40P7XK9392 (Flumazenil)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 6RZ6XEZ3CR (Chlordiazepoxide)
SB  - IM
MH  - Animals
MH  - Chick Embryo
MH  - Chlordiazepoxide/*pharmacology
MH  - Flumazenil/pharmacology
MH  - Neurons/drug effects/metabolism/physiology
MH  - Receptors, GABA-A/*drug effects/physiology
MH  - Spinal Cord/*drug effects/metabolism/physiology
MH  - gamma-Aminobutyric Acid/*physiology
PMC - PMC6569231
EDAT- 1988/03/01 00:00
MHDA- 1988/03/01 00:01
PMCR- 1988/09/01
CRDT- 1988/03/01 00:00
PHST- 1988/03/01 00:00 [pubmed]
PHST- 1988/03/01 00:01 [medline]
PHST- 1988/03/01 00:00 [entrez]
PHST- 1988/09/01 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.08-03-00814.1988 [doi]
PST - ppublish
SO  - J Neurosci. 1988 Mar;8(3):814-20. doi: 10.1523/JNEUROSCI.08-03-00814.1988.