Abstract
Bradykinin stimulates [ 3H]thymidine incorporation and DNA synthesis in resting, serum-deprived NIL8 hamster cells. The ED 50 for this stimulation is 4.52 ± 2.91 nM. Other kinin peptides including lys-bradykinin (kallidin) and met-lys-bradykinin also stimulate [ 3H]thymidine incorporation in the NIL8 cells, whereas desarg 9-bradykinin is without effect, suggesting action of the kinin peptides through type B 2 receptors. Bradykinin also stimulates DNA synthesis in IMR-90 human fibroblasts; however, this effect is observed only in the presence of indomethacin, which blocks prostaglandin synthesis. These results suggest that prostaglandins act as negative modulators of the growth-stimulatory effects of bradykinin in the fibroblasts. This conclusion is supported by the observation that exogenously added PGE 1, PGE 2, PGA 1, PGA 2, PGB 1, and PGB 2 strongly inhibit [ 3H]thymidine incorporation in the human fibroblasts. The direct effect of bradykinin observed in the NIL8 cells may be attributable to the relative resistance of these cells to growth inhibition by prostaglandins.
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