Mechanisms of Adenosine Release in the Developing and Adult Mouse Hippocampus

Adenosine is a neuromodulator known to inhibit the synaptic release of neurotransmitters, e.g., glutamate, and to hyperpolarize postsynaptic neurons. The release of adenosine is markedly enhanced under ischemic conditions. It may then act as an endogenous neuroprotectant against cerebral ischemia and excitotoxic neuronal damage. The mechanisms by which adenosine is released from nervous tissue are not fully known, particularly in the immature brain. We now characterized the release of [³H]adenosine from hippocampal slices from developing (7-day-old) and adult (3-month-old) mice using a superfusion system. The properties of the release differed only partially in the immature and mature hippocampus. The K⁺-evoked release was Ca²⁺ and Na⁺ dependent. Anion channels were also involved. Ionotropic glutamate receptor agonists potentiated the release in a receptor-mediated manner. Activation of metabotropic glutamate receptors enhanced the release in developing mice, with group II receptors alone being effective. The evoked adenosine release apparently provides neuroprotective effects against excitotoxicity under cell-damaging conditions. Taurine had no effect on adenosine release in adult mice, but depressed the release concentration dependently in the immature hippocampus.