Hashimoto Terumasa, Ohata Hisayuki, Honda Kazuo
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
J Pharmacol Sci. 2006 Jan;100(1):82-7. doi: 10.1254/jphs.fpj05030x. Epub 2006 Jan 11.
Lysophosphatidic acid (LPA), the simplest of the water-soluble phospholipids, can evoke various biological responses. The present study examined the activity of LPA to induce plasma exudation and histamine release in mice. Plasma exudation was assessed by extravasation of Evans blue. Subcutaneous administration of LPA (1 - 100 microg/site) led to increased plasma exudation in the skin. The LPA-induced plasma exudation was inhibited by ketotifen, a histamine H1-receptor antagonist, and diacylglycerol pyrophosphate (DGPP), a LPA1/LPA3-receptor antagonist. Moreover, pretreatment with pertussis toxin and DGPP inhibited the histamine release from peritoneal mast cells induced by LPA. These findings indicate that plasma exudation induced by LPA is mediated by histamine release from mast cells via LPA receptor(s), presumably LPA1 and/or LPA3, coupled to G(i/o) proteins. Moreover, these findings point to a role of LPA in the pathomechanisms of various allergic disorders.
溶血磷脂酸（LPA）是最简单的水溶性磷脂，可引发多种生物学反应。本研究检测了LPA诱导小鼠血浆渗出和组胺释放的活性。通过伊文思蓝外渗评估血浆渗出。皮下注射LPA（1 - 100微克/部位）导致皮肤血浆渗出增加。组胺H1受体拮抗剂酮替芬和LPA1/LPA3受体拮抗剂二酰甘油焦磷酸（DGPP）可抑制LPA诱导的血浆渗出。此外，百日咳毒素和DGPP预处理可抑制LPA诱导的腹膜肥大细胞组胺释放。这些发现表明，LPA诱导的血浆渗出是由肥大细胞通过LPA受体（可能是LPA1和/或LPA3）释放组胺介导的，这些受体与G(i/o)蛋白偶联。此外，这些发现表明LPA在各种过敏性疾病的发病机制中起作用。
