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The following are known triggers of mast cell degranulation (in addition to IgG activation via pathogen or allergen):[ref] Acetylcholine Complement fragments (C3, C4, C5) Various drugs, environmental toxins (MRGPRX2 receptor, details below) Peptides (including endorphin, leptin, PTH, and more) Physical conditions (cold, heat, pressure, stress, and vibration)