Activation of phosphoinositide hydrolysis by nerve growth factor and lysophosphatidylserine in rat peritoneal mast cells.
Histamine secretion in rat peritoneal mast cells stimulated by nerve growth factor requires a synergistic signal delivered by lysophosphatidylserine. To study the signal-transducing system activated by these compounds, phospholipid metabolism has been investigated in these cells. Phospholipid labeling with 32PO4 reveals a 5-9-fold stimulation of phosphatidic acid, phosphatidylinositol and phosphatidylcholine synthesis. Increased synthesis of phosphatidylinositol is also monitored using [3H]inositol incorporation. When [3H]inositol-labeled mast cells are incubated in the presence of Li+, nerve growth factor and lysophosphatidylserine enhance the accumulation of inositol monophosphate, inositol bisphosphate and inositol trisphosphate. Similar to the induced histamine release, accumulation of inositol phosphates (a) does not occur when the two agonists are added separately; (b) is inhibited when lysophosphatidyl-L-serine is replaced by lysophosphatidyl-D-serine; and (c) is enhanced in the presence of extracellular Ca2+. The data suggest that the interactive stimulus of nerve growth factor and lysophosphatidylserine is transmitted through the polyphosphoinositide-phospholipase C system.
Bellini
F
F
Department of Pharmacology, Fidia Research Laboratories, Padova, Italy.
Toffano
G
G
Bruni
A
A
D000818:Animals; D002118:Calcium / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D006868:Hydrolysis; D008246:Lysophospholipids / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008246:Lysophospholipids; D009414:Nerve Growth Factors; D010716:Phosphatidylinositols; C025059:lysophosphatidylserine; D002118:Calcium