Signalling mechanism in the lysophosphatidylserine-induced activation of mouse mast cells.
Lysophosphatidylserine (0.1-1 microM) elicits histamine release in isolated mouse peritoneal mast cells. The effect becomes manifest after a lag of 30 s and reaches completion in 5 min. Maximal activity is observed when serine is in L-configuration. As shown by the activity of a lysophosphatidylserine analogue lacking the OH group in C2 position of glycerol, conversion into phosphatidylserine is not required. When 32PO4-labeled mast cells are challenged 2-5 min with lysophosphatidylserine, the labeling of phosphatidate, phosphatidylinositol and phosphatidylcholine is increased. When [3H]arachidonate-labeled mast cells are used, lysophosphatidylserine increases the appearance of isotopic diacylglycerol and phosphatidate. Like the secretory response, these effects are independent of the presence of extracellular Ca2+. Incubations in the presence of [3H]glycerol show that lysophosphatidylserine does not activate the de novo synthesis of phospholipids. In agreement with a participation of phosphoinositidase C in the action of lysophosphatidylserine, we observe accumulation of inositol phosphates in [3H]inositol labeled mast cells incubated in the presence of Li+. The results suggest that lysophosphatidylserine delivers its stimulus to mast cells, by the activation of phosphoinositide-dependent signalling mechanism.
Fidia Research Laboratories, Abano Terme, Padova, Italy.
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D000215:Acylation; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002250:Carbon Radioisotopes; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010743:Phospholipids / Q000096:biosynthesis; D011865:Radioisotope Dilution Technique; D015398:Signal Transduction; D014316:Tritium
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D008246:Lysophospholipids; D010743:Phospholipids; C025059:lysophosphatidylserine; D014316:Tritium; D016718:Arachidonic Acid; D007294:Inositol