AI Article Synopsis
- Astrocytes regulate synaptic transmission by modulating extracellular GABA levels through specific GABA transporters (GAT-1 and GAT-3).
- The study reveals that the adenosine receptors A1R and A2AR can modify GABA uptake by acting through a complex known as heteromers, which impact the signaling pathways via different G proteins.
- This new understanding highlights how adenosine influences neurotransmission at the tripartite synapse involving neurons and astrocytes.
Article Abstract
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 A1 (A1R) and A2A (A2AR) receptors. This regulation occurs through A1R-A2AR heteromers that signal via two different G proteins, Gs and Gi/0, and either enhances (A2AR) or inhibits (A1R) 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757138 | PMC |
| http://dx.doi.org/10.1007/s11302-013-9364-5 | DOI Listing |
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