Search

1 Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs). 2 In the presence or absence of extracellular Ca2+, methyl paraben (0.1 - 10 mM) increased [Ca2+]1. 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 10nM). methyl paraben (0.3- 3 mM) induced histamine release. However, a high concentration (10mM) of the agent did not increase the histamine release. 4 U73122 (0.1 and 0.5μM), 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 Ca2+-free solution. PLC inhibitors (U73I22 0.1 and 0.5μM, D609 1 - 10μM) inhibited the methyl paraben-induced increase in [Ca2+i. whereas U73343 (0.5 μM) did not. 6 Xestospongin C (2 - 20μM) and 2 aminoethoxydiphenyl borate (30 and 100μM), blockers of the inositol 1.4.5-trisphosphale (IP3) receptor, inhibited the methyl paraben-induced increase in [Ca2+]i in Ca2+-free solution. 7 in conclusion, methyl paraben causes an increase in [Ca 2+]i. which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms. [ABSTRACT FROM AUTHOR]

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 micro M), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 micro M), 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 micro M, D609 1-10 micro M) inhibited the methyl paraben-induced increase in [Ca(2+)](i), whereas U73343 (0.5 micro M) did not. 6 Xestospongin C (2-20 micro M) and 2 aminoethoxydiphenyl borate (30 and 100 micro 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. 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.