Skip to main content
Log in

Lysophosphatidic acid induces inositol phosphate and calcium signals in exocrine cells from the avian nasal salt gland

  • Articles
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

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 μmol/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 μmol/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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Benton, A.M., Gerrard, J.M., Michiel, T., Kindom, S.E. 1982. Are lysophosphatidic acids or phosphatidic acids involved in stimulus activation coupling in platelets? Blood 60:642–649

    Google Scholar 

  • Borut, A., Schmidt-Nielsen, K. 1963. Respiration of avian saltsecreting gland in tissue slice experiments. Am. J. Physiol. 204:573–581

    Google Scholar 

  • Bradford, M.M. 1976. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Coffey, R.J., Leof, E.B., Shipley, G.D., Moses, H.L. 1987. Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J. Cell. Physiol. 132:143–148

    Google Scholar 

  • Cook, S.J., Rubinfeld, B., Albert, I., McCormick, F. 1993. RapV12 antagonizes Ras-dependent activation of ERK1 and ERK2 by LPA and EGF in Rat-1 fibroblasts. EMBO J. 12:3475–3485

    Google Scholar 

  • Das, A.K., Hajra, A.K. 1992. Critical micellar concentrations of palmitoyl dihydroxyacetone phosphate and 1-palmitoyl-rac-glycerol 3-phosphate. J. Biol. Chem. 267:9731

    Google Scholar 

  • Durieux, M.E., Carlisle, S.J., Salafranca, M.N., Lynch, K.R. 1993. Responses to sphingosine-1-phosphate in X. laevis oocytes: similarities with lysophosphatidic acid signaling. Am. J. Physiol. 264: C1360-C1364

    Google Scholar 

  • Fain, J.N. 1990. Regulation of phosphoinositide-specific phospholipase C. Biochim. Biophys. Acta 1053:81–88

    Google Scholar 

  • Fisher, S.K., Hootman, S.R., Heacock, A.M., Ernst, S.A., Agranoff, B.W. 1983. Muscarinic stimulation of phospholipid turnover in dissociated avian salt gland cells. FEBS Lett. 155:43–46

    Google Scholar 

  • Grynkiewicz, G., Poenie, M., Tsien, R. Y. 1985. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260:3440–3450

    Google Scholar 

  • Haase, R., Wieder, T., Geilen, C.C., Reutter, W. 1991. The phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis in Madin-Carby canine kidney cells. FEBS Lett. 288:129–132

    Google Scholar 

  • Hildebrandt, J.-P., Shuttleworth, T.J. 1991. Inositol phosphates and [Ca2+]i signals in a differentiating exocrine cell. Am. J. Physiol. 261:C210-C217

    Google Scholar 

  • Hildebrandt, J.-P., Shuttleworth, T.J. 1992. Calcium-sensitivity of inositol 1,4,5-trisphosphate metabolism in exocrine cells from the avian salt gland. Biochem. J. 282:703–710

    Google Scholar 

  • Hildebrandt, J.-P., Shuttleworth, T.J. 1993. A Gq-type G protein couples muscarinic receptors to inositol phosphate and calcium signaling in exocrine cells from the avian salt gland. J. Membrane Biol. 133:183–190

    Google Scholar 

  • Hughes, A.R., Takemura, H., Putney, J.W. 1988. Kinetics of inositol 1,4,5-trisphosphate and inositol cyclic 1∶2,4,5-trisphosphate metabolism in intact rat parotid acinar cells. J. Biol. Chem. 263:10314–10319

    Google Scholar 

  • Jalink, K., van Corven, E.J., Moolenaar, W.H. 1990. Lysophosphatidic acid, but not phosphatidic acid, is a potent Ca2+-mobilizing stimulus for fibroblasts. J. Biol. Chem. 265:12232–12239

    Google Scholar 

  • Kumagai, N., Morii, N., Fujisawa, K., Yoshimasa, T., Nakao, K., Narumiya, S. 1993. Lysophosphatidic acid induces tyrosine phosphorylation and activation of MAP kinase and focal adhesion kinase in cultured Swiss 3T3 cells. FEBS Lett. 329:273–276

    Google Scholar 

  • Moolenaar, W.H., Jalink, K., van Corven, E.J. 1992. Lysophosphatidic acid: A bioactive phospholipid with growth factor-like activities. Rev. Physiol. Biochem. Pharmacol. 119:47–65

    Google Scholar 

  • Morris, A.J., Waldo, G.L., Downes, C.P., Harden, T.K. 1990. A receptor and G-protein-regulated polyphosphoinositide-specific phospholipase C from turkey erythrocytes. J. Biol. Chem. 265:13501–13507

    Google Scholar 

  • Putney, J.W. 1993. Excitement about calcium signaling in inexcitable cells. Science 262:676–678

    Google Scholar 

  • Ridley, A.J., Hall, A. 1992. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399

    Article  CAS  PubMed  Google Scholar 

  • Shiono, S., Kawamoto, K., Yoshida, N., Kondo, T., Inagami, T. 1993. Neurotransmitter release from lysophosphatidic acid stimulated PC12 cells: involvement of lysophosphatidic acid receptors. Biochem. Biophys. Res. Comm. 193:667–673

    Google Scholar 

  • Shuttleworth, T.J. 1990. Receptor-activated calcium entry in exocrine cells does not occur via agonist-sensitive intracellular pools. Biochem. J. 266:719–726

    Google Scholar 

  • Shuttleworth, T.J., Thompson, J.L. 1989. Intracellular [Ca2+] and inositol phosphates in avian nasal gland cells. Am. J. Physiol. 257:C1020-C1029

    Google Scholar 

  • Strathmann, M., Simon, M.I. 1990. G protein diversity: A distinct class of a subunits is present in vertebrates and invertebrates. Proc. Natl. Acad. Sci. USA 87:9113–9117

    Google Scholar 

  • Takemura, H., Hughes, A.R., Thastrup, O., Putney, J.W. 1989. Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells. J. Biol. Chem. 264:12266–12271

    Google Scholar 

  • Tigyi, G., Miledi, R. 1992. Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus occytes and neurite retraction in PC12 pheochromocytoma cells. J. Biol. Chem. 267: 21360–21367

    Google Scholar 

  • Van Corven, E.J., Groenink, A., Jalink, K., Eichholtz, T., Moolenaar, W.H. 1989. Lysophosphatidate-induced cell proliferation: identification and dissection of signaling pathways mediated by G proteins. Cell 59:45–54

    Google Scholar 

  • Van Corven, E.J., Hordijk, P., Medema, R.H., Bos, J.L., Moolenaar, W.H. 1993. Pertussis toxin-sensitive activation of p21ras by G protein-coupled receptor agonists in fibroblasts. Proc. Natl. Acad. Sci. USA 90:1257–1261

    Google Scholar 

  • Van Corven, E.J., van Rijswijk, A., Jalink, K., van der Bend, R.L., van Blitterswijk, W.J., Moolenaar, W.H. 1992. Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Biochem. J. 281:163–169

    Google Scholar 

  • Van der Bend, R.L., Brunner, J., Jalink, K., van Corven, E.J., Moolenaar, W.H., van Blitterswijk, W.J. 1992. Identification of a putative membrane receptor for the bioactive phospholipid, lysophosphatidic acid. EMBO J. 11:2495–2501

    Google Scholar 

  • Weltzien, H.U. 1979. Cytolytic and membrane-perturbing properties of lysophosphatidylcholine. Biochim. Biophys. Acta 559:259–287

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

I would like to thank Prof. Dr. I. Schulz for providing lab space and some of the equipment used in this study and Prof. Dr. T.J. Shuttleworth for his helpful comments on a draft of the manuscript. This study was supported by the Deutsche Forschungsgemeinschaft (Hi 448/ 2-1 and 2-2).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hildebrandt, J.P. Lysophosphatidic acid induces inositol phosphate and calcium signals in exocrine cells from the avian nasal salt gland. J. Membarin Biol. 144, 49–58 (1995). https://doi.org/10.1007/BF00238416

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00238416

Key words

Navigation