Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity.
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 micro 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 nM), but not the A receptor antagonist, 8-cyclopentyltheophylline (200 nM), prevented the neuronal cell death caused by exposure of rat cultured cerebellar granule neurons to fragment 25-35 of beta-amyloid protein (25 micro 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.
Dall'Igna
Oscar P
OP
Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Porciúncula
Lisiane O
LO
Souza
Diogo O
DO
Cunha
Rodrigo A
RA
Lara
Diogo R
DR
Dall'lgna
Oscar P
OP
D058917:Adenosine A2 Receptor Antagonists; D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002110:Caffeine / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000008:administration & dosage* / Q000627:therapeutic use; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C113041:amyloid beta-protein (35-25); C053907:8-cyclopentyl-1,3-dimethylxanthine; D002110:Caffeine; D013806:Theophylline