Cannabinoids Induce Cell Death and Promote P2X7 Receptor Signaling in Retinal Glial Progenitors in Culture

被引:0
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作者
Hércules Rezende Freitas
Alinny Rosendo Isaac
Thayane Martins Silva
Geyzzara Oliveira Ferreira Diniz
Yara dos Santos Dabdab
Eduardo Cosendey Bockmann
Marília Zaluar Passos Guimarães
Karin da Costa Calaza
Fernando Garcia de Mello
Ana Lucia Marques Ventura
Ricardo Augusto de Melo Reis
Guilherme Rapozeiro França
机构
[1] Universidade Federal do Rio de Janeiro,Laboratory of Neurochemistry, Institute of Biophysics Carlos Chagas Filho
[2] Centro Universitário IBMR,School of Health Sciences
[3] Universidade Federal Fluminense,Laboratory of Neurochemistry, Institute of Biology
[4] Universidade Federal do Estado do Rio de Janeiro,Biomedical Institute
[5] Universidade Federal Fluminense,Laboratory of Retina Neurobiology, Institute of Biology
[6] Universidade Federal do Rio de Janeiro,Laboratory of Molecular Pharmacology, Institute of Biomedical Sciences
来源
Molecular Neurobiology | 2019年 / 56卷
关键词
ATP; Endocannabinoid; Retina; P2X7 receptor; Müller glia; Calcium signaling;
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中图分类号
学科分类号
摘要
Development of progenitors in the embryonic retina is modulated by signaling molecules, and cannabinoid receptors are highly expressed in the early developing retina. Here, we investigated whether the CB1/CB2 receptor agonist WIN 5212-2 (WIN) modulated the proliferation, viability, and calcium responses in chick embryo retinal progenitors in culture. A decline in [3H]-thymidine incorporation was observed when cultures were incubated with 0.5–1.0 μM WIN, an effect that was mimicked by URB602 and URB597, inhibitors of the monoacylglycerol lipase and fatty acid amide hydrolase, respectively. A reduction in the number of proliferating cell nuclear antigen-positive nuclei was also noticed in WIN-treated cultures, suggesting that activation of cannabinoid receptors decreases the proliferation of cultured retinal progenitors. WIN (0.5–5.0 μM), but not capsaicin, decreased retinal cell viability, an effect that was blocked by CB1 and CB2 receptor antagonists and by the P2X7 receptor antagonist A438079, implicating this nucleotide receptor in the cannabinoid-mediated cell death. Treatment with WIN also induced an increase in mitochondrial superoxide and P2X7 receptor-mediated uptake of sulforhodamine B in the cultured cells. While a high proportion of cultured cells responded to glutamate, GABA, and 50 mM KCl with intracellular calcium shifts, very few cells responded to the activation of P2X7 receptors by ATP. Noteworthy, while decreasing the number of cells responding to glutamate, GABA, and KCl, treatment of the cultures with WIN induced a significant increase in the number of cells responding to 1 mM ATP, suggesting that activation of cannabinoid receptors primes P2X7 receptor calcium signaling in retinal progenitors in culture.
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页码:6472 / 6486
页数:14
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