Adenosine promotes neuronal recovery from reactive oxygen species induced lesion in rat hippocampal slices.
Reactive oxygen species (ROS) are believed to be involved in the pathogenesis of several neurological disorders. We now tested whether the endogenous neuroprotective substance, adenosine, attenuates the cell damage induced by ROS. In rat hippocampal slices, the xanthine oxidase (40 mU/ml) plus xanthine (1 mM) (X/XO) system produced a 27.8+/-7.3% (n=3) increase in ROS, measured by fluorimetry with 2',7'-dichlorodihydrofluorescein, a 246.9+/-18.4% (n=6) increase in the release of tritiated adenosine, and a decrease in synaptic transmission that fully recovered after washout. In the presence of the adenosine A(1) receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine (100 nM), X/XO induced a similar inhibition, however synaptic transmission only recovered to 70.7+/-5.8% of control (n=5). The blockade of A(2A) receptors was devoid of effect (n=4). Adenosine is released by ROS-generating systems, and attenuates the deleterious cellular consequences of ROS through A(1) receptor activation.
Almeida
Cláudia G
CG
Laboratory of Neurosciences, Faculty of Medicine of Lisbon, Avenue Prof Egas Moniz, 1649-028 Lisbon, Portugal.
de Mendonça
Alexandre
A
Cunha
Rodrigo A
RA
Ribeiro
J Alexandre
JA
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D005470:Fluorometry; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D043705:Receptor, Adenosine A2A; D009435:Synaptic Transmission / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine