Effects of methyl p ‐hydroxybenzoate (methyl paraben) on Ca 2+ concentration and histamine release in rat peritoneal mast cells

Mechanisms of methyl p ‐hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and histamine release in rat peritoneal mast cells (RPMCs). In the presence or absence of extracellular Ca 2+ , methyl paraben (0.1–10 m M ) increased [Ca 2+ ] i , in a concentration‐dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12‐myristate 13‐acetate (PMA) 3 and 10 n M ), methyl paraben (0.3–3 m M ) induced histamine release. However, a high concentration (10 m M ) of the agent did not increase the histamine release. U73122 (0.1 and 0.5 μ M ), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben‐induced histamine release in PMA‐pretreated RPMCs. U73343 (0.5 μ M ), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. In Ca 2+ ‐free solution, PLC inhibitors (U73122 0.1 and 0.5 μ M , D609 1–10 μ M ) inhibited the methyl paraben‐induced increase in [Ca 2+ ] i , whereas U73343 (0.5 μ M ) did not. Xestospongin C (2–20 μ M ) and 2 aminoethoxydiphenyl borate (30 and 100 μ M ), blockers of the inositol 1,4,5‐trisphosphate (IP 3 ) receptor, inhibited the methyl paraben‐induced increase in [Ca 2+ ] i in Ca 2+ ‐free solution. In conclusion, methyl paraben causes an increase in [Ca 2+ ] i , which may be due to release of Ca 2+ from storage sites by IP 3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms.British Journal of Pharmacology (2003) 139 , 381–387. doi: 10.1038/sj.bjp.0705248