Glutamate differently modulates excitatory and inhibitory adenosine receptors in neuronal and glial cells.
Adenosine is a neuromodulator which acts through adenosine receptors regulating functions such as inhibition of glutamate release. Adenosine A(1) and A(2A) receptor activations most often regulate opposing actions. Primary rat cortical neurons and rat C6 cells, an astrocytic derived cell line, were exposed to 100muM l-glutamate, and cell viability and transduction pathways mediated by both A(1) and A(2A) receptors were analyzed. Glutamate-induced excitotoxic damage was found only in cortical neurons, with C6 cells preserved. In C6 cells, adenosine A(1) and A(2A) receptors were increased and decreased, respectively. Consequently, A(1)-mediated adenylyl cyclase inhibition and A(2A)-mediated adenylyl cyclase stimulation were, respectively, increased and decreased after glutamate exposure. In cortical neurons, glutamate treatment increased both A(1) and A(2A) receptors. Moreover, adenylyl cyclase responsiveness to A(1) or A(2A) receptor agonists was heightened in these cells, in which pharmacological activation of AC induced cell death. Finally, activation of A(1) receptor or blockade of A(2A) receptor during glutamate treatment partially prevented the glutamate-induced cell death detected in cultured cortical neurons. Results show that adenosine receptors are regulated by glutamate, and that this regulation is dependent on the cell type, suggesting that adenosine receptors might be promising targets in the therapy against excitotoxic cell death.
Castillo
Carlos Alberto
CA
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha (UCLM), Avenida Camilo José Cela, 10, 13071 Ciudad Real, Spain.
León
David Agustín
DA
Ballesteros-Yáñez
Inmaculada
I
Albasanz
José Luis
JL
Martín
Mairena
M
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism* / Q000502:physiology; D043705:Receptor, Adenosine A2A / Q000378:metabolism* / Q000502:physiology
D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D018698:Glutamic Acid