Skip to main content
Log in

Signalling properties of lysophosphatidic acid in primary human skin fibroblasts: role of pertussis toxin-sensitive GTP-binding proteins

  • ORIGINAL ARTICLE
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

We have investigated the signalling properties of the naturally occuring intercellular signalling molecule lysophosphatidic acid (LPA) in primary human skin fibroblasts. LPA stimulated phospholipase C activity resulting in the formation of inositol 1,4,5-trisphosphate (IP3) which was accompanied by a concentration-dependent increase in intracelluar calcium concentration ([Ca2+]i). The increase in [Ca2+]i was subject to homologous desensitisation but not to heterologous desensitisation by sphingosine-1-phosphate. The half-maximal effect of LPA on the rise in [Ca2+]i was attained at 7–20 nM. IP3 formation and Ca2+ mobilisation were highly pertussis toxin (PTX)-sensitive (100% and 75%, respectively). LPA also inhibited forskolin-stimulated formation of cAMP, which was partially reversed (51%) when fibroblasts were pretreated with PTX. To directly test the involvement of guanine nucleotide-binding regulatory proteins (G proteins), LPA-induced binding of the stable GTP analogue GTPγS was measured. LPA induced an increase in GTPγS binding, which was completely inhibited by PTX, implicating the involvement of Gi-type G proteins in LPA signalling. Furthermore, LPA increased DNA synthesis and cell proliferation. Finally, LPA induced the migration of human skin fibroblasts, which in conjunction with the stimulation of cell growth strengthens the presumed involvement of LPA in wound healing and tissue regeneration. Both effects (cell growth and migration) were almost completely PTX-sensitive.

Overall, these investigations in primary cultures of human skin fibroblasts confirm and extend our knowledge about LPA signalling, suggesting a pivotal role of receptor coupled activation of Gi-type proteins at least in this cell type.

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.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Received: 21 June 1996 / Accepted: 19 September 1996

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pietruck, F., Busch, S., Virchow, S. et al. Signalling properties of lysophosphatidic acid in primary human skin fibroblasts: role of pertussis toxin-sensitive GTP-binding proteins. Naunyn-Schmiedeberg's Arch Pharmacol 355, 1–7 (1996). https://doi.org/10.1007/PL00004906

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/PL00004906

Navigation