Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors.
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.
Hashimoto
Terumasa
T
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. t-hashi@pharm.showa-u.ac.jp
Ohata
Hisayuki
H
Honda
Kazuo
K
D000818:Animals; D002199:Capillary Permeability; D011756:Diphosphates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D007665:Ketotifen / Q000494:pharmacology; D008246:Lysophospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D037342:Pertussis Toxin / Q000494:pharmacology; D010949:Plasma / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects*
D011756:Diphosphates; D006634:Histamine H1 Antagonists; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C408642:diacylglycerol pyrophosphate; D037342:Pertussis Toxin; D005990:Glycerol; C032881:lysophosphatidic acid; D007665:Ketotifen