Oxidised adenosine 5'-triphosphate, a P2X(7) 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 P2X(7) antagonist, oxidised ATP (oATP) was highly neurotoxic. This toxicity was inhibited by co-incubation with BzATP. These results demonstrate that oATP is a potent neurotoxin.
Craighead
M W
MW
School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Oxford Road, M13 9PT, Manchester, UK.
Middlehurst
K M
KM
LeFeuvre
R
R
Kimber
I
I
Rothwell
N J
NJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity*; D000345:Affinity Labels / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D066298:In Vitro Techniques; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7
D000345:Affinity Labels; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate