Oxidised adenosine 5′-triphosphate, a P2X7 antagonist, is toxic to rat cerebellar granule neurones in vitro

Adenosine 5 ' -triphosphate (ATP) acts as a neurotransmitter in the central nervous system. Extracellular ATP is also toxic to a number of cell types e.g. via its interaction with P2X membrane receptors, specifically the P2X(7) family member. These results have led to the hypothesis that elevated ATP levels may exacerbate damage during acute neurodegeneration [4]. The aim of this study was to examine the effects of ATP agonists and antagonists on cultured rat cerebellar granule neurones. Neither ATP, nor the P2X agonist benzoylbenzoyl-ATP (BzATP), were toxic when added to primary neurones. However, the P2X7 antagonist, oxidised ATP (oATP) was highly neurotoxic. This toxicity was inhibited by coincubation with BzATP. These results demonstrate that oATP is a potent neurotoxin. (C) 2001 Published by Elsevier Science Ireland Ltd.