2-Chloroadenosine attenuates NMDA, kainate, and quisqualate toxicity.
Excitatory amino acid (EAA)-induced cell death in the striatum is dependent upon intact glutamatergic afferents arising from the cerebral cortex. Through a mechanism possibly related to inhibition of glutamate release, adenosine receptor agonists attenuate EAA induced toxicity in the rat striatum. In the present study, we examined whether 2-chloroadenosine (2CLA), a stable adenosine analog, protects against toxicity induced by kainate (KA), quisqualate (QUIS), N-methyl-D-aspartate (NMDA), and ibotenate (IBO). In vivo intrastriatal injections of 2CLA (50 nmol) with each EAA tested provided a partial but significant protective effect versus injection of the EAA alone, as measured by striatal concentrations of gamma-aminobutyric acid (GABA) and substance P-like immunoreactivity (SP-LI). These results show that 2CLA attenuates both NMDA- and non-NMDA-mediated neuronal cell death.
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
S F
SF
Finn
K J
KJ
Swartz
M F
MF
Beal
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D007267:Injections; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016318:Quisqualic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D015762:2-Chloroadenosine; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D007608:Kainic Acid