Bradykinin stimulates DNA synthesis in competent Balb/c 3T3 cells and enhances inositol phosphate formation induced by platelet- derived growth factor

Abstract

Both platelet-derived growth factor (PDGF) and bradykinin were found to induce a growth response in Balb/c 3T3 cells. However, whereas PDGF brought about a five-fold increase in the incorporation of [ 3H]thymidine into DNA, the response to bradykinin was never more than 50%. When bradykinin was present simultaneously with sub-optimal concentrations of PDGF the response was about 15% greater than with PDGF alone. In contrast, if the cells were made competent by a 5 hr preincubation with PDGF which was then washed away, subsequent addition of bradykinin induced a more than two-fold increase in incorporation of [ 3H]thymidine into DNA compared with competent cells subsequently incubated with serum-free medium alone. Bradykinin also acted synergistically with insulin when the two agents were added simultaneously to competent cells. PDGF induced marked increases in the concentration of inositol phosphates at 30 min after stimulation, but by this time point any effect of bradykinin had disappeared. However, the simultaneous presence of PDGF and bradykinin induced increases at 30 min that were 50–100% greater than with PDGF alone. It is concluded that the pathways by which PDGF and bradykinin initiate a growth response in BALB/c 3T3 cells only partly overlap. Their actions on the synthesis of inositol phosphates exhibit distinctive temporal characteristics, but can be co-operative at 30 min and at earlier time intervals. This effect was found to be time-dependent, and developed over the first 5 min.