Effects of bradykinin and thrombin on prostaglandin formation, cell proliferation and collagen biosynthesis in human dental-pulp fibroblasts.
Bradykinin and thrombin caused a time- and dose-dependent stimulation of prostanoid biosynthesis in human dental-pulp fibroblasts, as assessed by the release of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin). The stimulatory effect of bradykinin and thrombin on PGE2 biosynthesis was maximal within 5-10 min. The concentration of bradykinin producing half-maximal stimulation (EC50) of PGE2 and prostacyclin formation was 10 nM. EC50 for thrombin-induced formation of PGE2 and prostacyclin were 0.05 and 0.2 U/ml, respectively. Bradykinin analogues with affinity to the bradykinin B2 receptor, but not those with affinity to the B1 receptor, caused a burst of PGE2 formation. The stimulatory action of bradykinin and thrombin on PGE2 biosynthesis was abolished by two structurally different cyclo-oxygenase inhibitors and significantly reduced by two corticosteroids. Thrombin dose-dependently enhanced the incorporation of [3H]-thymidine into DNA in pulpal fibroblasts by a mechanism that was unrelated to the effect on prostanoid biosynthesis. Bradykinin did not affect thymidine incorporation. Thrombin, but not bradykinin, stimulated the biosynthesis of type 1 collagen in the pulpal fibroblasts. The stimulatory effect of thrombin on collagen biosynthesis was not affected by cyclo-oxygenase inhibitors. These data show that human dental-pulp fibroblasts are equipped with receptors for bradykinin and thrombin linked to enhanced prostanoid biosynthesis. Occupancy of the thrombin receptors also leads to a prostaglandin-independent stimulation of cell proliferation and collagen biosynthesis.
Sundqvist
G
G
Department of Endodontics, University of Umeå, Sweden.
Rosenquist
J B
JB
Lerner
U H
UH
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D001920:Bradykinin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003782:Dental Pulp / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis*; D018002:Receptors, Bradykinin / Q000378:metabolism; D018179:Receptors, Thrombin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
D011453:Prostaglandins; D018002:Receptors, Bradykinin; D018179:Receptors, Thrombin; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; D011464:Epoprostenol; D013917:Thrombin; D015232:Dinoprostone; D001920:Bradykinin