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.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004622:Embryo, Mammalian; D005246:Feedback; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung; D011453:Prostaglandins / Q000096:biosynthesis; D014176:Protein Biosynthesis
D001095:Arachidonic Acids; D011453:Prostaglandins; C024626:bradykinin, des-Arg(9)-; D016718:Arachidonic Acid; D003094:Collagen; D001920:Bradykinin; D007213:Indomethacin