G. Sundqvist et al., EFFECTS OF BRADYKININ AND THROMBIN ON PROSTAGLANDIN FORMATION, CELL-PROLIFERATION AND COLLAGEN BIOSYNTHESIS IN HUMAN DENTAL-PULP FIBROBLASTS, Archives of oral biology, 40(3), 1995, pp. 247-256
Bradykinin and thrombin caused a time- and dose-dependent stimulation
of prostanoid biosynthesis in human dental-pulp fibroblasts, as assess
ed by the release of prostaglandin E(2) (PGE(2)) and 6-keto-prostaglan
din F-1 alpha (the stable breakdown product of prostacyclin). The stim
ulatory effect of bradykinin and thrombin on PGE(2) biosynthesis was m
aximal within 5-10 min. The concentration of bradykinin producing half
-maximal stimulation (EC(50)) of PGE(2) and prostacyclin formation was
10 nM. EC(50) for thrombin-induced formation of PGE(2) and prostacycl
in were 0.05 and 0.2 U/ml, respectively. Bradykinin analogues with aff
inity to the bradykinin B-2 receptor, but not those with affinity to t
he B-1 receptor, caused a burst of PGE(2) formation. The stimulatory a
ction of bradykinin and thrombin on PGE(2) biosynthesis was abolished
by two structurally different cyclo-oxygenase inhibitors and significa
ntly reduced by two corticosteroids. Thrombin dose-dependently enhance
d the incorporation of [H-3]-thymidine into DNA in pulpal fibroblasts
by a mechanism that was unrelated to the effect on prostanoid biosynth
esis. 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 bi
osynthesis was not affected by cyclo-oxygenase inhibitors. These data
show that human dental-pulp fibroblasts are equipped with receptors fo
r bradykinin and thrombin linked to enhanced prostanoid biosynthesis.
Occupancy of the thrombin receptors also leads to a prostaglandin-inde
pendent stimulation of cell proliferation and collagen biosynthesis.