Bradykinin inhibition of EGF- and PDGF-induced DNA synthesis in human fibroblasts

Research output: Contribution to journalArticle

Abstract

Bradykinin exhibits proliferative influences in several types of cells; however, in the present study, bradykinin did not promote DNA synthesis but actually inhibited the DNA synthesis induced by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) in human gingival fibroblasts (HGF). This dose-dependent inhibitory effect was a specific intracellular interaction in that increasing concentrations of EGF did not counteract the inhibitory actions of bradykinin when added at 100 nM. The phosphoinositide- calcium signaling cascade is a likely point of interaction for the inhibitory influences of bradykinin; however, no interactions between bradykinin and EGF were observed with the generation of inositol phosphates or intracellular calcium fluxes. The inhibitory influences of bradykinin do not appear to be the result of a transmodulation of the EGF receptor, since EGF-mediated autophosphorylation was not negatively affected by bradykinin. Bradykinin- stimulated prostaglandin E 2 (PGE 2 ) release was potentiated by EGF, and, in the presence of indomethacin, the inhibition of the EGF-induced DNA synthesis by bradykinin was minimized. The results presented demonstrate that bradykinin can inhibit EGF- and PDGF-induced DNA synthesis and suggest that PGE 2 synthesis is responsible for the observed bradykinin inhibition of EGF- induced DNA synthesis.

Details

Authors
External organisations
  • Oregon Health & Science University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • epidermal growth factor, platelet-derived growth factor, prostaglandin E, signal transduction, thymidine incorporation
Original languageEnglish
Pages (from-to)C477-C484
JournalAmerican Journal of Physiology: Cell Physiology
Volume265
Issue number2 34-2
Publication statusPublished - 1993 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes