Requirement for direct cross-talk between B1 and B2 kinin receptors for the proliferation of androgen-insensitive prostate cancer PC3 cells
(2003) In Biochemical Journal 371. p.581-587- Abstract
- Stimulation of endogenous kinin receptors promotes growth of androgen-independent prostate cancer PC3 cells via activation of the mitogenic extracellular-signal-regulated kinase (ERK) pathway. In the present study, we show that kinin-mediated mitogenic signalling and prostate-cell growth involves two subtypes of bradykinin (BK) receptors, B1R and B2R. Specific stimulation of either B1R or B2R by their respective agonists des-Arg(9)-BK and Lys-BK promoted ERK activation and cell growth, whereas selective blockade with specific antagonists des-Arg(9)-[Leu(8)]BK and Hoe 140 respectively obliterated this effect, indicating the presence of both receptor subtypes. However, blockade of B1R also inhibited B2R-mediated ERK activation and cell... (More)
- Stimulation of endogenous kinin receptors promotes growth of androgen-independent prostate cancer PC3 cells via activation of the mitogenic extracellular-signal-regulated kinase (ERK) pathway. In the present study, we show that kinin-mediated mitogenic signalling and prostate-cell growth involves two subtypes of bradykinin (BK) receptors, B1R and B2R. Specific stimulation of either B1R or B2R by their respective agonists des-Arg(9)-BK and Lys-BK promoted ERK activation and cell growth, whereas selective blockade with specific antagonists des-Arg(9)-[Leu(8)]BK and Hoe 140 respectively obliterated this effect, indicating the presence of both receptor subtypes. However, blockade of B1R also inhibited B2R-mediated ERK activation and cell growth, and, similarly, antagonism of B2R inhibited the B1R-mediated response. Furthermore, both B1R and B2R agonists promoted internalization of B1R, whereas both receptor antagonists blocked this effect. The B1R ligands des-Arg(9)-BK and des-Arg(9)-[Leu(8)]BK had no effect on the binding of BK to B2R, as demonstrated by radioligand competitive binding studies. However, blockade of either B1R or B2R impaired the ability of the reciprocal receptor to produce inositol phosphates, suggesting that the interaction between B1R and B2R is proximal to activation of phospholipase C. These results provide evidence for the existence of B1R-B2R complexes in prostate cancer PC3 cells and demonstrate that antagonism of one receptor interferes with the signalling ability of the other, possibly at the level of receptor-Galpha(q) protein coupling. Selective inhibition of B1R, which is up-regulated in injured and cancerous tissue, may be beneficial for the treatment of advanced prostate cancer. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1127831
- author
- Barki-Harrington, Liza ; Bookout, Angela L ; Wang, Gaofeng ; Lamb, Maria E ; Leeb-Lundberg, Fredrik LU and Daaka, Yehia
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemical Journal
- volume
- 371
- pages
- 581 - 587
- publisher
- Portland Press
- external identifiers
-
- scopus:0038301608
- ISSN
- 0264-6021
- DOI
- 10.1042/BJ20021708
- language
- English
- LU publication?
- yes
- id
- 4ec5e19c-aa8a-45e5-8e4d-4f3067cdc089 (old id 1127831)
- date added to LUP
- 2016-04-01 16:43:25
- date last changed
- 2022-01-28 21:39:32
@article{4ec5e19c-aa8a-45e5-8e4d-4f3067cdc089,
abstract = {{Stimulation of endogenous kinin receptors promotes growth of androgen-independent prostate cancer PC3 cells via activation of the mitogenic extracellular-signal-regulated kinase (ERK) pathway. In the present study, we show that kinin-mediated mitogenic signalling and prostate-cell growth involves two subtypes of bradykinin (BK) receptors, B1R and B2R. Specific stimulation of either B1R or B2R by their respective agonists des-Arg(9)-BK and Lys-BK promoted ERK activation and cell growth, whereas selective blockade with specific antagonists des-Arg(9)-[Leu(8)]BK and Hoe 140 respectively obliterated this effect, indicating the presence of both receptor subtypes. However, blockade of B1R also inhibited B2R-mediated ERK activation and cell growth, and, similarly, antagonism of B2R inhibited the B1R-mediated response. Furthermore, both B1R and B2R agonists promoted internalization of B1R, whereas both receptor antagonists blocked this effect. The B1R ligands des-Arg(9)-BK and des-Arg(9)-[Leu(8)]BK had no effect on the binding of BK to B2R, as demonstrated by radioligand competitive binding studies. However, blockade of either B1R or B2R impaired the ability of the reciprocal receptor to produce inositol phosphates, suggesting that the interaction between B1R and B2R is proximal to activation of phospholipase C. These results provide evidence for the existence of B1R-B2R complexes in prostate cancer PC3 cells and demonstrate that antagonism of one receptor interferes with the signalling ability of the other, possibly at the level of receptor-Galpha(q) protein coupling. Selective inhibition of B1R, which is up-regulated in injured and cancerous tissue, may be beneficial for the treatment of advanced prostate cancer.}},
author = {{Barki-Harrington, Liza and Bookout, Angela L and Wang, Gaofeng and Lamb, Maria E and Leeb-Lundberg, Fredrik and Daaka, Yehia}},
issn = {{0264-6021}},
language = {{eng}},
pages = {{581--587}},
publisher = {{Portland Press}},
series = {{Biochemical Journal}},
title = {{Requirement for direct cross-talk between B1 and B2 kinin receptors for the proliferation of androgen-insensitive prostate cancer PC3 cells}},
url = {{http://dx.doi.org/10.1042/BJ20021708}},
doi = {{10.1042/BJ20021708}},
volume = {{371}},
year = {{2003}},
}