1. 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). 2. In the presence or absence of extracellular Ca 2+, methyl paraben (0.1-10 mM) increased [Ca 2+] i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. 3. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA) 3 and 10 nM), methyl paraben (0.3-3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release. 4. U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. 5. In Ca 2+-free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1-10 μM) inhibited the methyl paraben-induced increase in [Ca 2+] i, whereas U73343 (0.5 μM) did not. 6. Xestospongin C (2-20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), 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. 7. 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.
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