Adenosine A2B receptor activation stimulates glucose uptake in the mouse forebrain.
Purinergic Signalling. 2015-10-07; 11(4): 561-569
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Lemos C(1), Pinheiro BS(1), Beleza RO(1), Marques JM(1), Rodrigues RJ(1)(2), Cunha RA(1)(3), Rial D(1), Köfalvi A(4)(5).
(1)CNC, Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504, Coimbra, Portugal.
(2)Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
(3)FMUC, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
(4)CNC, Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504, Coimbra, Portugal. .
(5)Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal. .
ATP consumption during intense neuronal activity leads to peaks of both
extracellular adenosine levels and increased glucose uptake in the brain. Here,
we investigated the hypothesis that the activation of the low-affinity adenosine
receptor, the A2B receptor (A(2B)R), promotes glucose uptake in neurons and
astrocytes, thereby linking brain activity with energy metabolism. To this end,
we mapped the spatiotemporal accumulation of the fluorescent-labelled
(2-NBDG), in superfused acute hippocampal slices of C57Bl/6j mice. Bath
application of the A(2B)R agonist BAY606583 (300 nM) triggered an immediate and
stable (>10 min) increase of the velocity of 2-NBDG accumulation throughout
hippocampal slices. This was abolished with the pretreatment with the selective
A(2B)R antagonist, MRS1754 (200 nM), and was also absent in A(2B)R null-mutant
mice. In mouse primary astrocytic or neuronal cultures, BAY606583 similarly
increased (3)H-deoxyglucose uptake in the following 20 min incubation period,
which was again abolished by a pretreatment with MRS1754. Finally, incubation of
hippocampal, frontocortical, or striatal slices of C57Bl/6j mice at 37 °C, with
either MRS1754 (200 nM) or adenosine deaminase (3 U/mL) significantly reduced
glucose uptake. Furthermore, A(2B)R blockade diminished newly synthesized
glycogen content and at least in the striatum, increased lactate release. In
conclusion, we report here that A(2B)R activation is associated with an instant
and tonic increase of glucose transport into neurons and astrocytes in the mouse
brain. These prompt further investigations to evaluate the clinical potential of
this novel glucoregulator mechanism.
PMID: 26446689 [Indexed for MEDLINE]