Journal
PURINERGIC SIGNALLING
Volume 9, Issue 3, Pages 433-449Publisher
SPRINGER
DOI: 10.1007/s11302-013-9364-5
Keywords
Adenosine heteromers; G protein coupling; GABA transporters; Astrocytes
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT)
- Spanish Ministerio de Ciencia y Tecnologia [SAF2008-03229-E, SAF2008-00146]
- PRIN
- Universita Politecnica delle Marche
- FCT [SFRH/BD/38099/2007]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/38099/2007] Funding Source: FCT
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Astrocytes play a key role in modulating synaptic transmission by controlling extracellular gamma-aminobutyric acid (GABA) levels via GAT-1 and GAT-3 GABA transporters (GATs). Using primary cultures of rat astrocytes, we show here that a further level of regulation of GABA uptake occurs via modulation of the GATs by the adenosine A(1) (A(1)R) and A(2A) (A(2A)R) receptors. This regulation occurs through A(1)R-A(2A)R heteromers that signal via two different G proteins, G(s) and G(i/0), and either enhances (A(2A)R) or inhibits (A(1)R) GABA uptake. These results provide novel mechanistic insight into how GPCR heteromers signal. Furthermore, we uncover a previously unknown mechanism where adenosine, in a concentration-dependent manner, acts via a heterocomplex of adenosine receptors in astrocytes to significantly contribute to neurotransmission at the tripartite (neuron-glia-neuron) synapse.
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