Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells.
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.
Fukugasako
Sanae
S
Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
Ito
Shinichi
S
Ikemoto
Yoshimi
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D004342:Drug Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D010226:Parabens / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology
D015220:Calcium Channels; D004963:Estrenes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D010226:Parabens; D011760:Pyrrolidinones; D018160:Receptors, Cytoplasmic and Nuclear; C108644:xestospongin A; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C015358:methylparaben; D010738:Type C Phospholipases; D002118:Calcium