Long-term activation of adenosine A(2a) receptors blocks glutamate excitotoxicity in cultures of avian retinal neurons

Brain Research
J M Ferreira, Roberto Paes-de-Carvalho

Abstract

Previous work showed the presence of adenosine receptors as well as adenosine uptake and release mechanisms in developing chick retinal neurons in culture. In the present work we show that exogenous glutamate or kainate promotes extensive cell death in these cultures which is blocked when the cultures are previously incubated with adenosine. Addition of glutamate or kainate to purified cultures of retinal neurons and photoreceptors induced massive death of cultured cells which was inhibited in both cases by preincubation with MK801, an NMDA antagonist, or DNQX, an AMPA/kainate antagonist. Cell death was also greatly attenuated by preincubation with adenosine plus EHNA, an adenosine deaminase inhibitor, NBI, an adenosine uptake blocker, the permeable cAMP analogs 8-Br cAMP and Sp cAMP and the A(2a) agonists CGS 21680 and DPMA, but not with the A(1) receptor agonist CHA. Kinetic studies performed determining the intracellular LDH activity showed that maximal death was observed after 8 h and in concentrations of glutamate as low as 50 microM. We also observed a time-dependent protective effect of adenosine beginning after 1 h of preincubation and reaching a maximal effect after 24 h, indicating its association with changes in cell...Continue Reading

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Citations

Nov 16, 2002·Progress in Retinal and Eye Research·Masami Watanabe, Yutaka Fukuda
Mar 30, 2010·Acta Physiologica·J A Ribeiro, A M Sebastião
Apr 2, 2004·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Takashi Konno
Jul 11, 2013·PloS One·Joana VindeirinhoPaulo F Santos
Jan 31, 2014·International Journal of Molecular Sciences·Sandeep ShethVickram Ramkumar
Oct 16, 2002·Anais Da Academia Brasileira De Ciências·Roberto Paes-De-Carvalho
Apr 23, 2005·Progress in Retinal and Eye Research·Rafael LindenMariana S Silveira
Nov 25, 2003·Journal of Neuroscience Research·Shun WatanabeMasahiko Ikekita
Feb 5, 2005·Stroke; a Journal of Cerebral Circulation·Hui ShenYun Wang
Nov 12, 2019·Frontiers in Microbiology·Claudio Cesar Cirne-SantosIzabel Christina Nunes de Palmer Paixão
Jun 11, 2009·British Journal of Pharmacology·Ana M Sebastião, Joaquim A Ribeiro
Feb 23, 2020·Purinergic Signalling·D Pereira-FigueiredoK C Calaza
Mar 16, 2017·Journal of Neurochemistry·Edwin K JacksonPatrick M Kochanek
Dec 12, 2020·Free Radical Biology & Medicine·Camila C PortugalRoberto Paes-de-Carvalho
Sep 30, 2019·Neurochemistry International·Vladimir Pedro Peralva Borges-MartinsRegina Célia Cussa Kubrusly
Feb 29, 2020·Pharmacology & Therapeutics·Ana Raquel SantiagoAntónio Francisco Ambrósio
Aug 18, 2021·Expert Opinion on Therapeutic Targets·Puneet Agarwal, Renu Agarwal

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