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. 1990 Oct;101(2):382–386. doi: 10.1111/j.1476-5381.1990.tb12718.x

Evidence for BK1 bradykinin-receptor-mediated prostaglandin formation in osteoblasts and subsequent enhancement of bone resorption.

O Ljunggren 1, U H Lerner 1
PMCID: PMC1917693  PMID: 2175234

Abstract

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.

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Selected References

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  1. Barabé J., Babiuk C., Regoli D. Binding of [3H]des-Arg9-BK to rabbit anterior mesenteric vein. Can J Physiol Pharmacol. 1982 Dec;60(12):1551–1555. doi: 10.1139/y82-229. [DOI] [PubMed] [Google Scholar]
  2. Churchill L., Ward P. E. Relaxation of isolated mesenteric arteries by des-Arg9-bradykinin stimulation of B1 receptors. Eur J Pharmacol. 1986 Oct 14;130(1-2):11–18. doi: 10.1016/0014-2999(86)90178-0. [DOI] [PubMed] [Google Scholar]
  3. Deblois D., Bouthillier J., Marceau F. Effect of glucocorticoids, monokines and growth factors on the spontaneously developing responses of the rabbit isolated aorta to des-Arg9-bradykinin. Br J Pharmacol. 1988 Apr;93(4):969–977. doi: 10.1111/j.1476-5381.1988.tb11487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guimarães J. A., Vieira M. A., Eich E., Maack T. Effects of kinins on the isolated perfused rat kidney and evidence for the presence of renal B1 receptors. Adv Exp Med Biol. 1986;198(Pt A):559–562. doi: 10.1007/978-1-4684-5143-6_74. [DOI] [PubMed] [Google Scholar]
  5. Gustafson G. T., Lerner U. Bradykinin stimulates bone resorption and lysosomal-enzyme release in cultured mouse calvaria. Biochem J. 1984 Apr 1;219(1):329–332. doi: 10.1042/bj2190329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lerner U. H., Jones I. L., Gustafson G. T. Bradykinin, a new potential mediator of inflammation-induced bone resorption. Studies of the effects on mouse calvarial bones and articular cartilage in vitro. Arthritis Rheum. 1987 May;30(5):530–540. doi: 10.1002/art.1780300507. [DOI] [PubMed] [Google Scholar]
  7. Lerner U. H. Modifications of the mouse calvarial technique improve the responsiveness to stimulators of bone resorption. J Bone Miner Res. 1987 Oct;2(5):375–383. doi: 10.1002/jbmr.5650020504. [DOI] [PubMed] [Google Scholar]
  8. Lerner U. H., Ransjö M., Ljunggren O. Bradykinin stimulates production of prostaglandin E2 and prostacyclin in murine osteoblasts. Bone Miner. 1989 Jan;5(2):139–154. doi: 10.1016/0169-6009(89)90092-5. [DOI] [PubMed] [Google Scholar]
  9. Ljunggren O., Rosenquist J., Ransjö M., Lerner U. H. Bradykinin stimulates prostaglandin E2 formation in isolated human osteoblast-like cells. Biosci Rep. 1990 Feb;10(1):121–126. doi: 10.1007/BF01116860. [DOI] [PubMed] [Google Scholar]
  10. Nasjletti A., Malik K. U. Relationships between the kallikrein-kinin and prostaglandin systems. Life Sci. 1979 Jul 9;25(2):99–109. doi: 10.1016/0024-3205(79)90380-1. [DOI] [PubMed] [Google Scholar]
  11. Regoli D. C., Marceau F., Lavigne J. Induction of beta 1-receptors for kinins in the rabbit by a bacterial lipopolysaccharide. Eur J Pharmacol. 1981 Apr 24;71(1):105–115. doi: 10.1016/0014-2999(81)90391-5. [DOI] [PubMed] [Google Scholar]
  12. Regoli D., Marceau F., Barabé J. De novo formation of vascular receptors for bradykinin. Can J Physiol Pharmacol. 1978 Aug;56(4):674–677. doi: 10.1139/y78-109. [DOI] [PubMed] [Google Scholar]
  13. Regoli F., Del Chiaro R., Lunardi M., Farnesi A., Carnesecchi C., Bolognese L., Cordoni M., Giusti C. Comportamento delle extrasistoli nella prova da sforzo. Boll Soc Ital Cardiol. 1981;26(12):1979–1988. [PubMed] [Google Scholar]
  14. Rhaleb N. E., Dion S., Barabé J., Rouissi N., Jukic D., Drapeau G., Regoli D. Receptors for kinins in isolated arterial vessels of dogs. Eur J Pharmacol. 1989 Mar 29;162(3):419–427. doi: 10.1016/0014-2999(89)90332-4. [DOI] [PubMed] [Google Scholar]
  15. Vavrek R. J., Stewart J. M. Competitive antagonists of bradykinin. Peptides. 1985 Mar-Apr;6(2):161–164. doi: 10.1016/0196-9781(85)90033-6. [DOI] [PubMed] [Google Scholar]

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