CB1 receptor activation induces intracellular Ca2+ mobilization and 2-arachidonoylglycerol release in rodent spinal cord astrocytes

Scientific Reports
Zoltán HegyiMiklós Antal

Abstract

Accumulating evidence supports the role of astrocytes in endocannabinoid mediated modulation of neural activity. It has been reported that some astrocytes express the cannabinoid type 1 receptor (CB1-R), the activation of which is leading to Ca2+ mobilization from internal stores and a consecutive release of glutamate. It has also been documented that astrocytes have the potential to produce the endocannabinoid 2-arachidonoylglycerol, one of the best known CB1-R agonist. However, no relationship between CB1-R activation and 2-arachidonoylglycerol production has ever been demonstrated. Here we show that rat spinal astrocytes co-express CB1-Rs and the 2-arachidonoylglycerol synthesizing enzyme, diacylglycerol lipase-alpha in close vicinity to each other. We also demonstrate that activation of CB1-Rs induces a substantial elevation of intracellular Ca2+ concentration in astrocytes. Finally, we provide evidence that the evoked Ca2+ transients lead to the production of 2-arachidonoylglycerol in cultured astrocytes. The results provide evidence for a novel cannabinoid induced endocannabinoid release mechanism in astrocytes which broadens the bidirectional signaling repertoire between astrocytes and neurons.

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Citations

Feb 1, 2019·International Journal of Molecular Sciences·Shotaro Michinaga, Yutaka Koyama
Oct 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ferenc ZádorLászló Vécsei
Nov 5, 2020·Cell Chemical Biology·Aurélien LaguerreCarsten Schultz
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Mar 20, 2021·Nature Neuroscience·Eva Maria Meier CarlsenJean-François Perrier
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Sep 29, 2019·Journal of the American Chemical Society·Aurélien LaguerreCarsten Schultz
Aug 14, 2021·The Journal of Comparative Neurology·Ariana Z Turk, Shahriar SheikhBahaei

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