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Neuroprotection by caffeine and adenosine A 2A receptor blockade of β ‐amyloid neurotoxicity
Author(s) -
Dall'lgna Oscar P,
Porciúncula Lisiane O,
Souza Diogo O,
Cunha Rodrigo A,
Lara Diogo R
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705185
Subject(s) - neuroprotection , neurotoxicity , adenosine receptor , adenosine , adenosine receptor antagonist , caffeine , receptor , chemistry , pharmacology , antagonist , adenosine a1 receptor , receptor antagonist , adenosine a2a receptor , propidium iodide , neuroscience , endocrinology , biology , programmed cell death , biochemistry , apoptosis , toxicity , agonist , organic chemistry
Adenosine is a neuromodulator in the nervous system and it has recently been observed that pharmacological blockade or gene disruption of adenosine A 2A receptors confers neuroprotection under different neurotoxic situations in the brain. We now observed that coapplication of either caffeine (1–25 μ M ) or the selective A 2A receptor antagonist, 4‐(2‐[7‐amino‐2(2‐furyl)(1,2,4)triazolo (2,3‐ a )(1,3,5)triazin‐5‐ylamino]ethyl)phenol (ZM 241385, 50 n M ), but not the A receptor antagonist, 8‐cyclopentyltheophylline (200 n M ), prevented the neuronal cell death caused by exposure of rat cultured cerebellar granule neurons to fragment 25–35 of β ‐amyloid protein (25 μ M for 48 h), that by itself caused a near three‐fold increase of propidium iodide‐labeled cells. This constitutes the first in vitro evidence to suggest that adenosine A 2A receptors may be the molecular target responsible for the observed beneficial effects of caffeine consumption in the development of Alzheimer's disease. British Journal of Pharmacology (2003) 138 , 1207–1209. doi: 10.1038/sj.bjp.0705185