Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity

Oscar P Dall'Igna; Lisiane O Porciúncula; Diogo O Souza; Rodrigo A Cunha; Diogo R Lara

doi:10.1038/sj.bjp.0705185

Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity

Br J Pharmacol. 2003 Apr;138(7):1207-9. doi: 10.1038/sj.bjp.0705185.

Authors

Oscar P Dall'Igna¹, Lisiane O Porciúncula, Diogo O Souza, Rodrigo A Cunha, Diogo R Lara

Affiliation

¹ Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Abstract

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.

Publication types

Editorial
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine A2 Receptor Antagonists*
Alzheimer Disease / etiology*
Alzheimer Disease / pathology*
Amyloid beta-Peptides / pharmacology
Amyloid beta-Peptides / toxicity*
Animals
Brain / drug effects
Brain / pathology
Caffeine / pharmacology*
Cells, Cultured / drug effects
Central Nervous System Diseases / chemically induced*
Cerebellum / cytology
Cerebellum / drug effects
Neurons / drug effects
Neuroprotective Agents / pharmacology*
Peptide Fragments / pharmacology
Rats
Rats, Wistar
Receptor, Adenosine A2A / administration & dosage*
Receptor, Adenosine A2A / therapeutic use
Theophylline / analogs & derivatives*
Theophylline / pharmacology
Triazines / pharmacology
Triazoles / pharmacology

Substances

Adenosine A2 Receptor Antagonists
Amyloid beta-Peptides
Neuroprotective Agents
Peptide Fragments
Receptor, Adenosine A2A
Triazines
Triazoles
ZM 241385
amyloid beta-protein (35-25)
8-cyclopentyl-1,3-dimethylxanthine
Caffeine
Theophylline