PMID- 22180742
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121002
LR  - 20211021
IS  - 1662-6427 (Electronic)
IS  - 1662-6427 (Linking)
VI  - 3
DP  - 2011
TI  - Activation of astroglial calcium signaling by endogenous metabolites succinate 
      and gamma-hydroxybutyrate in the nucleus accumbens.
PG  - 7
LID - 10.3389/fnene.2011.00007 [doi]
LID - 7
AB  - Accumulating evidence suggests that different energy metabolites play a role not 
      only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) 
      transients evoked by the major citric acid cycle metabolite succinate (SUC) and 
      gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been 
      described in the brain reward area, the nucleus accumbens (NAc). Cells responding 
      to SUC by Ca(2+) transient constitute a subset of ATP-responsive astrocytes that 
      are activated in a neuron-independent way. In this study we show that GHB-evoked 
      Ca(2+) transients were also found to constitute a subset of ATP-responsive 
      astrocytes in the NAc. Repetitive Ca(2+) dynamics evoked by GHB suggested that 
      Ca(2+) was released from internal stores. Similarly to SUC, the GHB response was 
      also characterized by an effective concentration of 50 muM. We observed that the 
      number of ATP-responsive cells decreased with increasing concentration of either 
      SUC or GHB. Moreover, the concentration dependence of the number of 
      ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], 
      suggesting a mutual receptor for SUC and GHB, therefore implying the existence of 
      a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked 
      Ca(2+) signal remained in mice lacking GABA(B) receptor type 1 subunit in the 
      presence and absence of the N-Methyl-d-Aspartate (NMDA) receptor antagonist 
      (2R)-amino-5-phosphonovaleric acid (APV), indicating action mechanisms 
      independent of the GABA(B) or NMDA receptor subtypes. By molecular docking 
      calculations we found that residues R99, H103, R252, and R281 of the binding 
      crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91) also 
      predict interaction with GHB, further implying similar GHB and SUC action 
      mechanisms. We conclude that the astroglial action of SUC and GHB may represent a 
      link between brain energy states and Ca(2+) signaling in astrocytic networks.
FAU - Molnar, Tunde
AU  - Molnar T
AD  - Department of Neurochemistry, Chemical Research Center, Hungarian Academy of 
      Sciences Budapest, Hungary.
FAU - Heja, Laszlo
AU  - Heja L
FAU - Emri, Zsuzsa
AU  - Emri Z
FAU - Simon, Agnes
AU  - Simon A
FAU - Nyitrai, Gabriella
AU  - Nyitrai G
FAU - Pal, Ildiko
AU  - Pal I
FAU - Kardos, Julianna
AU  - Kardos J
LA  - eng
PT  - Journal Article
DEP - 20111212
PL  - Switzerland
TA  - Front Neuroenergetics
JT  - Frontiers in neuroenergetics
JID - 101477960
PMC - PMC3235779
OTO - NOTNLM
OT  - astroglial calcium signaling
OT  - energy metabolites
OT  - gamma-hydroxybutyrate
OT  - nucleus accumbens
OT  - succinate
EDAT- 2011/12/20 06:00
MHDA- 2011/12/20 06:01
PMCR- 2011/01/01
CRDT- 2011/12/20 06:00
PHST- 2011/10/22 00:00 [received]
PHST- 2011/11/25 00:00 [accepted]
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2011/12/20 06:01 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - 10.3389/fnene.2011.00007 [doi]
PST - epublish
SO  - Front Neuroenergetics. 2011 Dec 12;3:7. doi: 10.3389/fnene.2011.00007. 
      eCollection 2011.