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 phosph ate generation and calcium signals as well as rearrangements of the cy toskeleton and mitogenic responses in fibroblasts, for its ability to activate phospholipase C in an exocrine cell system, the salt-secretin g cells from the avian nasal salt gland. LPA (>10 nmol/l) caused the g eneration of inositol phosphates from membrane-bound phosphatidylinosi tides. The resulting calcium signals resembled those generated upon ac tivation of muscarinic receptors, the physiological stimulus triggerin g salt secretion in these cells. However, close examination of the LPA -mediated calcium signals revealed that the initial calcium spike indu ced by high concentrations of LPA (>10 mu mol/l) may contain a compone nt that is not dependent upon generation of inositol (1,4,5)-trisphosp hate (Ins(1,4,5)P-3) and may result from calcium influx from the extra cellular medium induced by LPA in a direct manner. Low concentrations of LPA (<10 mu mol/l), however, induce inositol phosphate generation, Ins(1,4,5)P-3-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 phospholi pase 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 t rigger hydrolysis of the same pool of phosphatidylinositol (4,5)-bisph osphate (PIP2) and mobilize calcium from the same intracellular stores .