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P2Y 13 and P2X 7 receptors modulate mechanically induced adenosine triphosphate release from mast cells
Author(s) -
Shen Dan,
Shen Xueyong,
Schwarz Wolfgang,
Grygorczyk Ryszard,
Wang Lina
Publication year - 2020
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14093
Subject(s) - ppads , p2 receptor , suramin , p2y receptor , purinergic receptor , adenosine , receptor , purinergic signalling , microbiology and biotechnology , adenosine triphosphate , receptor antagonist , adenosine a2b receptor , adenosine receptor , chemistry , biology , endocrinology , agonist , antagonist , biochemistry
Subcutaneous mast cells (MCs) are vulnerable to mechanical stimulation from external environment. Thus, MCs immune function could be modulated by their mechanosensitivity. This property has been identified as the trigger mechanism of needling acupuncture, a traditional oriental therapy. Previously we have demonstrated the release of adenosine triphosphate (ATP), a stress‐responsive signalling molecule, from mechanical‐perturbed MCs. The current work explores its underlying mechanisms. We noticed that propagation of intracellular free Ca 2+ occurred among HMC‐1 cells in response to 50% hypotonic shock. Additionally, amplifying cascade of ATP‐induced ATP release was observed in RBL‐2H3 cells stimulated by medium displacement, which could be mimicked by exogenous ATP (exoATP). Secondary ATP liberation induced by low level (50 nmol/L) of exoATP was reduced by inhibiting ecto‐ATPase‐dependent ADP production with ARL67156, or blocking P2 receptors with suramin or PPADS, or with specific P2Y 13 receptor antagonist MRS2211, or siRNA. Secondary ATP release induced by higher dose (200 μmol/L) of exoATP, sufficient to stimulate P2X 7 receptor, was attenuated by suramin, PPADS or specific P2X 7 receptor antagonist BBG, or siRNA. Finally, RT‐PCR confirmed mRNA expression of P2Y 13 and P2X 7 in RBL‐2H3 cells. Additionally, such secondary ATP release was attenuated by DPCPX, specific antagonist of adenosine A1 receptor, but not by MRS2179, specific inhibitor of P2Y 1 receptor. In summary, mechanosensitive ATP release from MCs is facilitated by paracrine/autocrine stimulation of P2Y 13 and P2X 7 receptors. This multi‐receptor combination could mediate transmission of information from a local site to distal areas, enabling communication with multiple surrounding cells to coordinate and synchronize their function.