Bradykinin inhibition of EGF- and PDGF-induced DNA synthesis in human fibroblasts.
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 E2 (PGE2) 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 PGE2 synthesis is responsible for the observed bradykinin inhibition of EGF-induced DNA synthesis.
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
B S
BS
McAllister
F
F
Leeb-Lundberg
M S
MS
Olson
D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D010716:Phosphatidylinositols / Q000502:physiology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015398:Signal Transduction; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D004815:Epidermal Growth Factor; D004247:DNA; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium