PMID- 18539266
OWN - NLM
STAT- MEDLINE
DCOM- 20081008
LR  - 20220310
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1219
DP  - 2008 Jul 11
TI  - Brain-derived neurotrophic factor inhibits GABA uptake by the rat hippocampal 
      nerve terminals.
PG  - 19-25
LID - 10.1016/j.brainres.2008.04.008 [doi]
AB  - The lifespan of the predominant inhibitory neurotransmitter in the central 
      nervous system, gamma-aminobutyric acid (GABA), is determined by its uptake into 
      neurons and glia, through high-affinity Na(+)/Cl(-) dependent transporters 
      (GATs). We now evaluated how the uptake of GABA by nerve endings, which is mostly 
      mediated by the GAT-1 subtype, is modulated by brain-derived neurotrophic factor 
      (BDNF). BDNF (10-200 ng/ml) decreased GAT-1-mediated GABA uptake by isolated 
      hippocampal rat nerve terminals (synaptosomes), an effect that occurred within 1 
      min of incubation with BDNF and blocked by the tyrosine kinase inhibitor K252a 
      (100 nM) as well as by the PLC inhibitor, U73122 (3 microM). Maximum inhibition 
      was attained with 100 ng/ml BDNF. In contrast with what has been observed for 
      other synaptic actions of BDNF, the inhibition of GABA transport by BDNF does not 
      require tonic activation of adenosine A(2A) receptors since it was not blocked by 
      the A(2A) receptor antagonist SCH 58261 (50 nM). However, in synaptosomes 
      previously depleted of extracellular endogenous adenosine by incubation with 
      adenosine deaminase (1 U/ml), activation of A(2A) receptors with the A(2A) 
      receptor agonist, CGS 21680 (30 nM), enhanced the inhibitory effect of BDNF upon 
      GABA transport, an action prevented by the A(2A) receptor antagonist, SCH 58261 
      (50 nM). It is concluded that BDNF, through TrkB and PLCgamma signalling inhibits 
      GAT-1-mediated GABA transport by nerve endings and that this action is not 
      dependent on, but can be enhanced by, TrkB/A(2A) receptor cross talk.
FAU - Vaz, Sandra H
AU  - Vaz SH
AD  - Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of 
      Neuroscience, Institute of Molecular Medicine, University of Lisbon, Portugal.
FAU - Cristovao-Ferreira, Sofia
AU  - Cristovao-Ferreira S
FAU - Ribeiro, Joaquim A
AU  - Ribeiro JA
FAU - Sebastiao, Ana M
AU  - Sebastiao AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080416
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phenethylamines)
RN  - 10028-17-8 (Tritium)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/analogs & derivatives/pharmacology
MH  - Adenosine Deaminase/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/*ultrastructure
MH  - Phenethylamines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Synaptosomes/*drug effects/*metabolism
MH  - Time Factors
MH  - Tritium/metabolism
MH  - gamma-Aminobutyric Acid/*metabolism
EDAT- 2008/06/10 09:00
MHDA- 2008/10/09 09:00
CRDT- 2008/06/10 09:00
PHST- 2007/11/06 00:00 [received]
PHST- 2008/04/03 00:00 [revised]
PHST- 2008/04/04 00:00 [accepted]
PHST- 2008/06/10 09:00 [pubmed]
PHST- 2008/10/09 09:00 [medline]
PHST- 2008/06/10 09:00 [entrez]
AID - S0006-8993(08)00887-1 [pii]
AID - 10.1016/j.brainres.2008.04.008 [doi]
PST - ppublish
SO  - Brain Res. 2008 Jul 11;1219:19-25. doi: 10.1016/j.brainres.2008.04.008. Epub 2008 
      Apr 16.