Neuroprotection during hypoxic insults: Role of adenosine

Adenosine is released from neurones and from glial cells during hypoxic and ischaemic episodes, and, by operating membrane A? receptors, acts as a neuroprotective agent. Evidence for this neuroprotective role of adenosine is supplied by both in vivo and in vitro studies. By evaluating the action of hypoxia on synaptic transmission in hippocampal slices, it has been shown that substances that are also released during hypoxia, such as gamma -aminobutyric acid (GABA), acetylcholine, and even glutamate may also have a neuroprotective role; however their action is evident only when activation of adenosine A(1) receptors is impaired. We propose that adenosine A(1) receptors have a pivotal role during hypoxia, though other substances can operate in a redundant or even overprotective manner, acting as a substitute for some adenosine actions when the nucleoside is not operative. Drug Dev. Res. 52:291-295, 2001. (C) 2001 Wiley-Liss, Inc.