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Lysophosphatidic acid induces histamine release from mast cells and skin fragments
Terumasa Hashimoto1, Hisayuki Ohata, Kazutaka Momose
1Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Abstract:
The present study examined whether lysophosphatidic acid (LPA) induces histamine release and the role of Rho-associated protein kinase (ROCK) in histamine release utilizing Y-27632, an inhibitor of ROCK. Rat peritoneal mast cells and mouse skin fragments were challenged with LPA; subsequently, histamine contents were measured by spectrofluorometric assay. LPA-induced histamine release from mast cells and skin fragments occurred in a time- and dose-dependent manner Pretreatment with Y-27632 inhibited LPA-induced histamine release in a dose-dependent fashion. LPA-induced histamine release was not influenced by calcium-free conditions; however, A23187-induced histamine release decreased significantly. TMB-8, an intracellular calcium antagonist, dose-dependently inhibited the histamine release under these conditions. Additionally, Y-27632 scarcely affected A23187-induced histamine release. These findings suggest that LPA-induced histamine release may be attributable to calcium release from intracellular stores. Moreover, ROCK participates in the extracellular calcium-independent process of LPA-induced histamine release.
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