scholarly journals P2X7 on mast cells participates in peripheral pain and serves as a potential target for salicylic acid and aspirin analgesia

2021 ◽  
Author(s):  
Yucui Jiang ◽  
Fan Ye ◽  
Ying Du ◽  
Zongxiang Tang
Keyword(s):  
Salicylic Acid ◽  
Mast Cells ◽  
Calcium Imaging ◽  
P2x7 Receptor ◽  
Inflammatory Factors ◽  
Binding Region ◽  
High Concentration ◽  
Peritoneal Mast Cells ◽  
Peripheral Pain

Abstract Background Extracellular ATP signaling through excitatory and calcium-permeable P2X receptor channels is considered as a critical player in pain generation and maintenance. P2X7 has attracted much attention over the past decade because of its prominent role in driving inflammatory processes. The role of P2X7 in mast cells in peripheral pain remains unclear.Methods P2X expression in mouse peritoneal mast cells was detected by RT-PCR. The subtypes of P2X receptors in mouse peritoneal mast cells were determined with a series of blockers by using calcium imaging and electrophysiology. The regulation of inflammatory factors mediated by different P2X subtypes were detected by ELISA and real-time PCR. The role of mast cells and P2X7 receptor in peripheral pain was explored by behavioral assays, pathological analysis and real-time PCR. Several anti-inflammatory small molecules were screened based on P2X7 in mast cells by using calcium imaging, electrophysiology and molecular docking.Results We found that ATP was significantly increased in inflammatory pain. Mouse peritoneal mast cells expressed P2X1, P2X3, P2X4 and P2X7 and could be activated by different concentrations of extracellular ATP, which could be blocked by specific ion channel antagonists. In particularly, high concentration of ATP could induce mast cells to release inflammatory mediators such as histamine, IL-1β and CCL3 through P2X7 receptor. Furthermore, peripheral pain induced by high concentration of ATP could be alleviated by P2X7 blockers or mast cell defects. Interestingly, salicylic acid and aspirin could attenuate the inward current, the release of inflammatory factors and peripheral pain induced by ATP with high concentration. Furthermore, salicylic acid and aspirin also inhibited the inward current evoked by P2X7 agonist BZATP. Molecular docking results showed that salicylic acid and aspirin had affinity to the cytoplasmic GDP-binding region of P2X7.Conclusions We concluded that P2X7 on mast cells involved in peripheral pain. Salicylic acid and aspirin could inhibit the activity of P2X7 via interacting with the GDP binding region. P2X7 receptor was a potential target for salicylic acid and aspirin analgesia.

scholarly journals P2X7 on Mast Cells Participates in Peripheral Pain and Serves as A Potential Target for Salicylic Acid and Aspirin Analgesia

2020 ◽  
Author(s):  
Yucui Jiang ◽  
Fan Ye ◽  
Ying Du ◽  
Zongxiang Tang
Keyword(s):  
Mast Cell ◽  
Salicylic Acid ◽  
Mast Cells ◽  
Inflammatory Mediators ◽  
P2x7 Receptor ◽  
P2x Receptors ◽  
Extracellular Atp ◽  
High Concentration ◽  
Peritoneal Mast Cells ◽  
Peripheral Pain

Abstract Background Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. ATP is an important molecule closely related to many important physiological and pathologic functions. ATP-gated cation channel P2X receptors are widely distributed in various tissues of body, including nervous system and immune system. As an important member of P2X receptors, P2X7 is not only involved in pain, epilepsy, Parkinson’s diseases, but also in the formation of blood, respiratory and digestive diseases. In this study, we investigated the role of P2X receptors in mast cells for peripheral pain and the analgesic mechanism of salicylic acid and aspirin. Methods P2X receptors were examined and identified in mouse peritoneal mast cells by RT-PCR, intracellular calcium measurement and electrophysiology. The inflammatory mediators released from the activated mast cell were examined by real-time PCR and ELISA. Paw swelling, mechanical stimulation threshold and histopathological changes were tested to evaluate the peripheral pain in mice.Results The results showed that P2X1, P2X4, P2X7 receptors were expressed in mouse peritoneal mast cells. Mast cell was activated in a concentration-dependent manner by extracellular ATP, and the activation could be blocked by specific ion channel antagonists. In addition, high concentrations of ATP also induced mast cells to release inflammatory mediators such as histamine, IL-1β and CCL3 through P2X7 receptor. Furthermore, peripheral pain of the extracellular high concentration ATP to induce could be alleviated by P2X7 blockers or mast cell defects. We also found that salicylic acid and its derivation aspirin could inhibit high concentration ATP-induced inward current, release of inflammatory factors in mast cells, as well as the peripheral pain caused by high concentration ATP. Conclusions Together with these, we concluded that extracellular ATP with high concentration could not only activate neurons directly, but also activate P2X7 receptor on mast cells, and induce peripheral pain via neuro-immune crosstalk. Additionally, salicylic and aspirin could inhibit the activity of P2X7, therefore, P2X7 receptor may be one of the potential targets for salicylic acid and aspirin analgesia.

Role of common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of murine mast cells

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2172-2180 ◽  
Author(s):  
Kotaro Suzuki ◽  
Hiroshi Nakajima ◽  
Norihiko Watanabe ◽  
Shin-ichiro Kagami ◽  
Akira Suto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Cytokine Receptor ◽  
Type I ◽  
Dependent Manner ◽  
Type Ii ◽  
Wild Type ◽  
Peritoneal Mast Cells ◽  
The Common

Abstract The regulatory roles of the common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of mast cells were determined using γc-deficient (γc−) and Jak3-deficient (Jak3−) mice. Although the mast cells in γc− and Jak3− mice were morphologically indistinguishable from those in wild-type mice, the number of peritoneal mast cells was decreased in γc− and Jak3− mice as compared with that in wild-type mice. Among γc-related cytokines, interleukin (IL)-4 and IL-9, but not IL-2, IL-7, or IL-15, enhanced the proliferation and survival of bone marrow–derived mast cells (BMMCs) from wild-type mice. However, the effects of IL-4 and IL-9 were absent in BMMCs from γc− and Jak3−mice. In addition, IL-4Rα, γc, and Jak3, but not IL-2Rβ or IL-7Rα, were expressed in BMMCs. In contrast, IL-13 did not significantly induce the proliferation and survival of BMMCs even from wild-type mice, and IL-13Rα1 was not expressed in BMMCs. Furthermore, IL-4 phosphorylated the 65-kd isoform of Stat6 in BMMCs from wild-type mice but not from γc− and Jak3− mice. These results indicate that γc- and Jak3-dependent signaling is essential for IL-4– and IL-9–induced proliferation and survival of murine mast cells, that the effects of IL-4 are mediated by type I IL-4R and that type II IL-4R is absent on mast cells, and that IL-4 phosphorylates the 65-kd isoform of Stat6 in mast cells in a γc- and Jak3-dependent manner.

Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells

2001 ◽  
Vol 425 (3) ◽  
pp. 229-238 ◽  
Author(s):  
Kheng H. Peh ◽  
Andrew Moulson ◽  
Beatrice Y.C. Wan ◽  
El-Sayed K. Assem ◽  
Frederick L. Pearce
Keyword(s):  
Nitric Oxide ◽  
Mast Cells ◽  
Histamine Release ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells ◽  
Human Basophils

scholarly journals Evidence for a role of phosphatidylinositol turnover in stimulus–secretion coupling. Studies with rat peritoneal mast cells

1979 ◽  
Vol 178 (3) ◽  
pp. 681-687 ◽  
Author(s):  
Shamshad Cockcroft ◽  
Bastien D. Gomperts
Keyword(s):  
Mast Cells ◽  
Concanavalin A ◽  
Immunoglobulin E ◽  
Histamine Secretion ◽  
Phosphatidylinositol Turnover ◽  
Phosphatidylinositol Response ◽  
Peritoneal Mast Cells ◽  
Stimulus Secretion Coupling ◽  
Rat Peritoneal Mast Cells

Histamine secretion and phosphatidylinositol turnover were compared in antigen-sensitized rat peritoneal mast cells stimulated with a number of different ligands. A small and variable increase in the incorporation of [32P]Pi and of [3H]inositol into phosphatidylinositol was observed when the cells were treated with immunoglobulin E-directed ligands (antigens and concanavalin A), and this was accompanied by a low amount of secretion (<10% of total cell histamine). In the presence of added phosphatidylserine, the addition of immunoglobulin E-directed ligands invariably led to an enhanced rate (approx. 4-fold) of labelling of phosphatidylinositol and, in the presence of Ca2+, this was accompanied by the secretion of histamine. The labelling of phosphatidylinositol and histamine secretion were also stimulated by chymotrypsin and compound 48/80. Whereas the phosphatidylinositol response did not require the presence of extracellular Ca2+, the secretion of histamine was either enhanced or dependent on extracellular Ca2+ (depending on the ligand used). The dependence on ligand concentration for the phosphatidylinositol response and histamine secretion were similar. The increased isotopic incorporation into phosphatidylinositol continued for about 1h although histamine secretion (elicited with concanavalin A) stopped within 2min. These results support the proposition that metabolic events involving phosphatidylinositol play a necessary intermediate role in the regulation of Ca2+ channels by ligand-activated receptors.

scholarly journals Role of membrane skeleton in the degranulation of rat peritoneal mast cells.

1994 ◽  
Vol 64 ◽  
pp. 92
Author(s):  
Mitsunobu Mio ◽  
Kiyomi Miyake ◽  
Masako Yamaji ◽  
Kenji Tasaka
Keyword(s):  
Mast Cells ◽  
Membrane Skeleton ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

073 A role of vesicles during degranulation of chymase from rat peritoneal mast cells

1995 ◽  
Vol 10 (1) ◽  
pp. 75
Author(s):  
M. Aoki ◽  
M. Honda ◽  
O. Kawanami ◽  
G. Login ◽  
A. Dvorak
Keyword(s):  
Mast Cells ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

scholarly journals Mast cells are responsible for the lack of anti-inflammatory effects of morphine in CBA mice

2004 ◽  
Vol 13 (5-6) ◽  
pp. 365-368 ◽  
Author(s):  
Elzbieta Stankiewicz ◽  
Ewa Wypasek ◽  
Barbara Plytycz
Keyword(s):  
Mast Cells ◽  
Histamine Release ◽  
Swiss Mice ◽  
Cba Mice ◽  
Peritoneal Mast Cells ◽  
Anti Inflammatory ◽  
Zymosan Peritonitis

BACKGROUND and aim: Morphine co-injection has anti-inflammatory effects on zymosan-induced peritonitis in several strains of mice except that of CBA. As peritoneal mast cells (pMCs) are much more numerous in CBA mice than in SWISS mice, the role of pMCs in morphine-modulated zymosan peritonitis is compared in CBA and SWISS males.Methods: pMCs were treatedin vitrowith morphine or C48/80 for comparison of histamine release.In vivoaccumulation of leukocytes and histamine in peritoneal exudate were recorded after intraperitoneal injection with morphine, zymosan, or zymosan plus morphine.Results and conclusion: Morphine induces histamine release by pMCs from CBA mice but not SWISS mice.In vivomorphine-induced peritonitis is stronger in CBA mice than SWISS mice. Corollary, morphine anti-inflammatory effects on zymosan peritonitis are reversed in CBA mice by its pro-inflammatory action through CBA pMCs.

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