Lysophosphatidic acid induces inositol phosphate and calcium signals in exocrine cells from the avian nasal salt gland.
We tested lysophosphatidic acid (LPA) known to induce inositol phosphate generation and calcium signals as well as rearrangements of the cytoskeleton and mitogenic responses in fibroblasts, for its ability to activate phospholipase C in an exocrine cell system, the salt-secreting cells from the avian nasal salt gland. LPA (> 10 nmol/l) caused the generation of inositol phosphates from membrane-bound phosphatidylinositides. The resulting calcium signals resembled those generated upon activation of muscarinic receptors, the physiological stimulus triggering salt secretion in these cells. However, close examination of the LPA-mediated calcium signals revealed that the initial calcium spike induced by high concentrations of LPA (> 10 mumol/l) may contain a component that is not dependent upon generation of inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) and may result from calcium influx from the extracellular medium induced by LPA in a direct manner. Low concentrations of LPA (< 10 mumol/l), however, induce inositol phosphate generation, Ins(1,4,5)P3-mediated release of calcium from intracellular pools and calcium entry. These effects seem to be mediated by a specific plasma membrane receptor and a G protein transducing the signal to phospholipase C in a pertussis-toxin-insensitive manner. Signaling pathways of the muscarinic receptor and the putative LPA-receptor seem to merge at the G-protein level as indicated by the fact that carbachol and LPA trigger hydrolysis of the same pool of phosphatidylinositol (4,5)-bisphosphate (PIP2) and mobilize calcium from the same intracellular stores.
Hildebrandt
J P
JP
Physiologisches Institut, Medizinische Fakultät, Universität des Saarlandes, Homburg/Saar, FRG.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004372:Ducks; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007295:Inositol Phosphates / Q000502:physiology*; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D012491:Salt Gland / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D008246:Lysophospholipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D001285:Atropine; D002217:Carbachol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium