Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors

Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors
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DOI:
10.1254/jphs.fpj05030x
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发表时间:
2006-01-01
影响因子:
3.5
通讯作者:
Honda, K
Honda, K
中科院分区:
医学3区
文献类型:
--
作者:
Hashimoto, T;Ohata, H;Honda, K

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溶血磷脂酸(LPA)是最简单的水溶性磷脂,可引起多种生物反应。本研究检测了LPA诱导小鼠血浆渗出和组胺释放的活性。Evans蓝外渗评估血浆渗出。皮下注射LPA (1-100 μ g/位点)导致皮肤血浆渗出增加。组胺h -1受体拮抗剂酮替芬和LPA(1)/LPA(3)受体拮抗剂二酰基焦磷酸甘油(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释放组胺。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LPA(1)和/或LPA(3))偶联G(i/o)蛋白释放组胺介导的。此外,这些发现指出LPA在各种过敏性疾病的病理机制中的作用。
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 mu g/site) led to increased plasma exudation in the skin. The LPA-induced plasma exudation was inhibited by ketotifen, a histamine H-1-receptor antagonist, and diacylglycerol pyrophosphate (DGPP), a LPA(1)/LPA(3)-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 LPA(1) and/or LPA(3), coupled to G(i/o) proteins. Moreover, these findings point to a role of LPA in the pathomechanisms of various allergic disorders.