Bradykinin-2 receptor-mediated release of 3H-arachidonic acid and formation of prostaglandin E2 in human gingival fibroblasts.
Bradykinin stimulated production of prostaglandin E2 (PGE2) and the release of 3H-arachidonic acid by gingival fibroblasts in a time- and dose-dependent manner. The effect on PGE2 biosynthesis was seen already after 15 seconds and was maximal after 5 minutes. Several structurally unrelated inhibitors of arachidonic acid metabolism via the cyclooxygenase pathway totally abolished the PGE2 response to bradykinin. The stimulation of PGE2 formation was seen at and above 10 nmol/l of bradykinin. Des-Arg9-bradykinin was 100-fold less potent compared to bradykinin. Des-Arg9-Leu8-bradykinin did not antagonize bradykinin-induced PGE2 formation. Met-Lys-bradykinin and Lys-bradykinin also enhanced PGE2 formation in gingival fibroblasts. The stimulatory action of bradykinin on 3H-arachidonic acid release was observed after 30 s and progressively increased for at least 15 min. The stimulatory effect on 3H-arachidonic acid release by bradykinin was seen at and above 10 nmol/l, whereas des-Arg9-bradykinin was without effect up to a concentration of 1 mumol/l. Indomethacin did not affect bradykinin-induced 3H-arachidonic acid release. These data show that bradykinin, via a B2-receptor-mediated pathway, can stimulate arachidonic acid release and subsequent prostanoid formation in gingival fibroblasts. Consequently, gingival fibroblasts may contribute, by a bradykinin-regulated reaction, to the enhanced amounts of prostanoids found in gingival tissues and crevicular fluids in patients with periodontal diseases.
Modéer
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Department of Pedodontics, Faculty of Odontology, Karolinska Institutet, Huddinge, Sweden.
Ljunggren
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Lerner
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UH
D000704:Analysis of Variance; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D005480:Flurbiprofen / Q000494:pharmacology; D005881:Gingiva / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007609:Kallidin / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology
D001095:Arachidonic Acids; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D016718:Arachidonic Acid; D007609:Kallidin; D008469:Meclofenamic Acid; C018103:bradykinin, Met-Lys-; D005480:Flurbiprofen; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin