Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges

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Nurkhametova , D , Kudryavtsev , I , Guselnikova , V , Serebryakova , M , Giniatullina , R R , Wojciechowski , S , Tore , F , Rizvanov , A , Koistinaho , J , Malm , T & Giniatullin , R 2019 , ' Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges ' , Frontiers in Cellular Neuroscience , vol. 13 , 45 . https://doi.org/10.3389/fncel.2019.00045

Title: Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges
Author: Nurkhametova, Dilyara; Kudryavtsev, Igor; Guselnikova, Valeriia; Serebryakova, Maria; Giniatullina, Raisa R.; Wojciechowski, Sara; Tore, Fatma; Rizvanov, Albert; Koistinaho, Jari; Malm, Tarja; Giniatullin, Rashid
Contributor: University of Helsinki, Neuroscience Center
Date: 2019-02-13
Language: eng
Number of pages: 12
Belongs to series: Frontiers in Cellular Neuroscience
ISSN: 1662-5102
URI: http://hdl.handle.net/10138/312730
Abstract: Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analyzed by the uptake of organic dye YO-PRO1 as well as 4,6-diamidino-2-phenylindole (DAPI). Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP). Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.
Subject: ATP
EXPRESSION
FUNCTIONAL-CHARACTERIZATION
MECHANISMS
MIGRAINE
P2X(7) RECEPTOR
P2X7 receptor
PAIN
PHARMACOLOGICAL CHARACTERIZATION
PORE FORMATION
RELEASE
degranulation
mast cells
migraine
neuroinflammation
3112 Neurosciences
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