Activation of protein formation and cell division by bradykinin and des-Arg9-bradykinin

We employed des-Arg9-bradykinin to investigate the relation between bradykinin-induced prostaglandin (PG) synthesis and bradykinin-induced protein accumulation. In this feedback control system, bradykinin-induced PG synthesis limits bradykinin-induced protein production. At low concentration (5 X 10(-8) M), des-Arg9-bradykinin was significantly less active than bradykinin in stimulating the formation of prostaglandins by human fetal lung fibroblasts in culture. At high concentration (5 X 10(-6) M), bradykinin induced a 24% increase in protein formation, while des-Arg9-bradykinin induced a 61% increase in collagen formation and an 80% increase in total protein accumulation. In the presence of indomethacin, bradykinin-induced protein formation was increased further, whereas des-Arg9-bradykinin-induced protein formation was unchanged. The bradykinin derivative increased the production of types I and III procollagens without affecting the distribution of procollagen types. The incorporation of [3H]thymidine into DNA in lung fibroblast cultures was increased 3-fold by des-Arg9-bradykinin alone or by bradykinin in combination with indomethacin. Des-Arg9-[Leu8]bradykinin inhibited the des-Arg9-bradykinin-induced protein formation and cell division. These data indicate that both bradykinin and des-Arg9-bradykinin stimulate protein formation and cell division; des-Arg9-bradykinin alone stimulates protein formation and cell division without activating PG synthesis and PG feedback control.