title: Sinomenine potentiates P815 cell degranulation via upregulation of Ca2+ mobilization through the Lyn/PLCγ/IP3R pathway.
abstract: Mast cells are vital mediators of drug allergy and, therefore, studying the relationship between drug allergy and mast cells is essential. Sinomenine is the principal active component of Sinomenium acutum, which has anti-inﬂammatory and anti-immune effects, and is used to treat various rheumatoid diseases. However, allergic responses to sinomenine are frequently reported. Therefore, this study assessed the effects of sinomenine on mast cell activation to characterize its allergic effects and the underlying mechanisms. Enzyme-linked immunosorbent assay (ELISA), western blot analyses, and degranulation assays were performed to measure pro-inﬂammatory and allergic mediators in P815 cells. The allergenic effects of sinomenine were also determined in mice by using active general anaphylaxis (ASA). The results indicated that sinomenine induced inositol-1,4,5-trisphosphate (IP3) production and the release of histamine, interleukin (IL)-6, and endoplasmic reticulum Ca2+in P815 cells. Furthermore, sinomenine upregulated the phosphorylation of sarcoma (Src), phospholipase C (PLC)-γ1, and IP3receptor (R). Therefore, sinomenine induced concentration-dependent mast cell activation directly in vitro Furthermore, our in vivo data identified an appropriate intravenous dose that did not induce these allergic effects, thereby providing information for the potential safe clinical use of sinomenine.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China helc@mail.xjtu.edu.cn.
authors.forename: Langchong
authors.initials: L
authors.lastname: He
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004342:Drug Hypersensitivity / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015850:Interleukin-6; D009019:Morphinans; C009271:sinomenine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D051966:Phospholipase C gamma; D002118:Calcium
keywords: anaphylaxis; degranulation; sinomenine