Bradykinin and thrombin stimulate release of arachidonic acid and formation of prostanoids in human periodontal ligament cells.
Previous reports have demonstrated the importance of prostaglandin formation in orthodontic tooth movement, but the mechanisms involved in the activation of prostaglandin biosynthesis in the periodontal ligament (PDL) are still unclear. There is, however, evidence that inflammatory reactions appear after application of orthodontic forces. In the present study, the effect of bradykinin (BK) and thrombin, two inflammatory mediators, on prostanoid biosynthesis in human PDL-cells was investigated. BK and thrombin caused a time-dependent burst of prostaglandin E2 (PGE2) formation (maximal effect after 2-5 min). The stimulatory actions of BK and thrombin on PGE2 biosynthesis were dose-dependent; seen in PDL-cells isolated from four different patients and abolished by the non-steroidal anti-inflammatory drug indomethacin. BK and thrombin also dose-dependently stimulated the biosynthesis of PGI2. BK agonists, with affinity to the B2 subtype of BK receptors, caused a significant increase of PGE2 biosynthesis in human PDL-cells. In contrast, BK agonists with affinity to BK-B1 receptors did not cause a burst of PGE2 biosynthesis. BK and BK-B2 receptor agonists as well as thrombin, but not BK-B1 receptor agonists, also significantly increased [3H] release in human PDL-cells prelabelled with [3H]-arachidonic acid, indicating that BK and thrombin stimulate prostanoid biosynthesis, at least partly, due to activation of phospholipase A2. These data show that BK via BK-B2 receptors, as well as thrombin, have the capacity to stimulate arachidonic acid release and subsequent prostanoid biosynthesis in human PDL-cells and thus may be implicated in the tissue reactions involved in orthodontic tooth movement.
Marklund
M
M
Department of Orthodontics, University of Umeå, Sweden.
Lerner
U H
UH
Persson
M
M
Ransjö
M
M
D000595:Amino Acid Sequence; D016718:Arachidonic Acid / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism; D015203:Reproducibility of Results; D013268:Stimulation, Chemical; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D018002:Receptors, Bradykinin; D016718:Arachidonic Acid; D011464:Epoprostenol; D013917:Thrombin; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin