Evidence for BK1 bradykinin-receptor-mediated prostaglandin formation in osteoblasts and subsequent enhancement of bone resorption.
1. The effects of the BK1 bradykinin (BK)-receptor agonist des-Arg9-BK on bone resorption and prostaglandin formation in osteoblasts have been studied. 2. Des-Arg9-BK (1 microM) stimulated the release of 45Ca from prelabelled neonatal mouse calvarial bones and the formation of prostaglandin E2 (PGE2) in calvarial bones. The stimulatory effect on bone resorption and PGE2 formation could be totally inhibited by indomethacin, flurbiprofen and hydrocortisone. 3. The BK1 receptor antagonist des-Arg9-Leu8-BK (10 microM) inhibited des-Arg9-BK (0.01-0.1 microM)-induced release of 45Ca from prelabelled neonatal mouse calvarial bones, while leaving BK (0.1-1 microM)-induced 45Ca release unaffected. 4. In isolated osteoblast-like cells from neonatal mouse calvarial bones, des-Arg9-BK (1 microM) induced a slowly developing increase in PGE2 formation that was significantly different from untreated controls after 24 h. Treatment with BK caused a rapid burst (within minutes) of PGE2 formation. 5. Des-Arg9-Leu8-BK (10 microM) selectively inhibited des-Arg9-BK (1 microM)-induced PGE2 and prostacyclin formation in isolated osteoblast-like cells incubated for 72 h. Des-Arg9-Leu8-BK did not affect BK and Lys-BK (1 microM)-induced PGE2 and prostacyclin formation in isolated osteoblast-like cells incubated for 72 h. 6. These data indicate that osteoblasts are equipped with BK1-receptors mediating enhanced prostaglandin formation and subsequent bone resorption.
Ljunggren
O
O
Department of Oral Pathology, University of Umeå, Sweden.
Lerner
U H
UH
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C024626:bradykinin, des-Arg(9)-; D015232:Dinoprostone; D001920:Bradykinin