1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus.
Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the N-methyl-D-aspartate (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 +/- 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 +/- 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 +/- 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 +/- 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 +/- 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8- cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory of Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal.
P
P
Canhão
A
A
de Mendonça
J A
JA
Ribeiro
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014970:Xanthines; D016202:N-Methylaspartate; C051360:1,3-dipropyl-8-cyclopentylxanthine