Adenosine is the major modulator of neuronal activity and neurovascular coupling in the brain, however the mechanism controlling adenosine tone is still to be determined. We have investigated adenosine release mechanism in rat slice preparation by using the adenosine sensor cell system (Morita et al, Neuro2013 abstract). Adenosine release was detected following high frequency electrical stimulation, potassium channel blocker treatment or hypoosmotic treatment. The electrically-evoked release alone was inhibited by L-type calcium channel blockers. Further pharmacological characterization has revealed that the electrically-evoked release depends on ryanodine receptor-mediated calcium-induced calcium release. Since neuronal L-type calcium channel is known to localize largely in dendrite, these results suggest that the source of the adenosine release following intense neuronal activity, which cause transient presynaptic inhibition of excitatory transmission, is dendrite. Meanwhile, the adenosine releases following potassium channel blockade, which likely caused astrocyte swelling, and hypoosmotic treatment were inhibited by blockers for astrocyte specific water channel, AQP4, and exto-ATPase. Thus, these adenosine increases are mediated by the breakdown of ATP released from swollen astrocytes. Recently, astrocytic exocytosis of ATP has been proposed to underlie adenosine build-up for sleep induction, however the triggering mechanism for this adenosine release is still to be determined. Our results suggest that humoral change causing astrocyte swelling induces the ATP exocytosis of astrocyte.