Extended Data Fig. 5: Activation of adenosine A2B receptors induces the release of lactate.
From: Adenosine signalling to astrocytes coordinates brain metabolism and function
(a) A representative recording of changes in lactate microelectrode biosensor current illustrating facilitated release of lactate in response to adenosine, recorded in an acute brain slice; (b) Summary data illustrating peak increases in the release of lactate recorded in acute brain slices in response to ATP, ATP in the presence of ZM241385 (10 µM) or PPADS (30 µM); adenosine, and adenosine in the presence of ZM241385 (10 µM), H89 (30 µM), an inhibitor of glycogen phosphorylase DAB (150 µM), or A1 adenosine receptor antagonist DPCPX (1 µM). P values, one-way ANOVA followed by Sidak’s post hoc test; (c) Averaged (means ± s.e.m.) traces illustrating the release of adenosine and lactate (recorded simultaneously using microelectrode biosensors) in response to neuronal network activation induced by application of AMPA (5 µM); (d) Averaged (means ± s.e.m.) traces and (e) summary data illustrating the effect of A2 receptor blockade with ZM241385 (10 µM) on AMPA-induced lactate release in acute brain slices. P value, two-tailed Student’s t-test; (f) Averaged (means ± s.e.m.) traces and summary data illustrating the release of lactate induced by A2B receptor agonist Bay 60-6583 (1 µM) in acute hippocampal slices prepared from the brains of Adora2bflox/flox:Aldh1l1Cre- and Adora2bflox/flox:Aldh1l1Cre/ERT2+ mice treated with tamoxifen. The effect of Bay 60-6583 on lactate release was markedly reduced by genetic deletion of A2B receptors in astrocytes. P value, two-tailed Student’s t-test. In the box-and-whisker plots, the central dot indicates the mean, the central line indicates the median, the box limits indicate the upper and lower quartiles, and the whiskers extend to 1.5 IQR from the quartiles. Numbers in parentheses indicate the number of independent slice experiments/number of animals per experimental group.
