Hashimoto Terumasa, Ohata Hisayuki, Momose Kazutaka, Honda Kazuo
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Pharmacology. 2005 Dec;75(1):13-20. doi: 10.1159/000085784. Epub 2005 May 13.
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.
