Article date: May 2003
By: Sanae Fukugasako, Shinichi Ito, Yoshimi Ikemoto in Volume 139, Issue 2, pages 381-387
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).
In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]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 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.
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.
In Ca2+‐free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben‐induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not.
Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5‐trisphosphate (IP3) receptor, inhibited the methyl paraben‐induced increase in [Ca2+]i in Ca2+‐free solution.
In conclusion, methyl paraben causes an increase in [Ca2+]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.
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).
In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]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 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.
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.
In Ca2+‐free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben‐induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not.
Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5‐trisphosphate (IP3) receptor, inhibited the methyl paraben‐induced increase in [Ca2+]i in Ca2+‐free solution.
In conclusion, methyl paraben causes an increase in [Ca2+]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.
British Journal of Pharmacology (2003) 139, 381–387. doi:10.1038/sj.bjp.0705248
DOI: 10.1038/sj.bjp.0705248
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