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Cannabinoid receptors couple to NMDA receptors to reduce the production of NO and the mobilization of zinc induced by glutamate.

Antioxid Redox Signal.. 2013-06; 
SÁnchez-BlÁzquez P, RodrÍguez-Muñoz M, Vicente-SÁnchez A, GarzÓn J. Department of Neuropharmacology, Cajal Institute, Consejo Superior de Investigaciones CientÍficas (CSIC), Madrid, Spain.
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Abstract Aims: Overactivation of glutamate N-methyl-D-aspartate receptor (NMDAR) increases the cytosolic concentrations of calcium and zinc, which significantly contributes to neural death. Since cannabinoids prevent the NMDAR-mediated increase in cytosolic calcium, we investigated whether they also control the rise of potentially toxic free zinc ions, as well as the processes implicated in this phenomenon. Results: The cannabinoid receptors type 1 (CNR1) and NMDARs are cross-regulated in different regions of the nervous system. Cannabinoids abrogated the stimulation of the nitric oxide-zinc pathway by NMDAR, an effect that required the histidine triad nucleotide-binding protein 1 (HINT1). Conversely, NMDAR ant... More

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