NDLI: Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to $Ca^{2+}$ Mobilization and Cell Proliferation

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Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to $Ca^{2+}$ Mobilization and Cell Proliferation

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Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to $Ca^{2+}$ Mobilization and Cell Proliferation

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Costa, Maria Adelina Correia-de-sá, Paulo Pinheiro, Ana Rita Certal, Mariana Ferreirinha, Fátima Paramos-de-carvalho, Diogo Costa, Cristina Magalhães-cardoso, Maria Teresa Sévigny, Jean
Description	Author Affiliation: Pinheiro AR ( From the Laboratório de Farmacologia e Neurobiologia, Unidade Multidisciplinar de Investigação Biomédica (UMIB), and.)
Abstract	Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca(2+) ([Ca(2+)]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca(2+)]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca(2+)]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with (10)Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca(2+)]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca(2+)]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	38
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-09-20
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenosine Triphosphate Secretion Calcium Metabolism Cell Proliferation Drug Effects Connexins Fibroblasts Histamine Agonists Pharmacology Histamine Nerve Tissue Proteins Adenosine Diphosphate Analogs & Derivatives Anti-Bacterial Agents Antimalarials Brefeldin A Cells, Cultured Collagen Type I Biosynthesis Antagonists & Inhibitors Exocytosis Physiology Cytology Gene Expression Regulation Mast Cells Mefloquine Octanols Purinergic P2Y Receptor Antagonists Receptors, Histamine H1 Receptors, Purinergic P2Y1 Clinical Trial Multicenter Study Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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