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Autoregulation of bradykinin receptors : Agonists in the presence of interleukin-1β shift the repertoire of receptor subtypes from B2 to B1 in human lung fibroblasts

Phagoo, Stephen B. ; Poole, Stephen and Leeb-Lundberg, L. M.Fredrik LU (1999) In Molecular Pharmacology 56(2). p.325-333
Abstract

Elevated formation of bradykinin (BK) and Lys-BK or kallidin (KD) and their carboxypeptidase metabolites desArg9BK and desArg10KD is evident at sites of inflammation. Moreover, B2 receptors (B2R) which mediate the action of BK and KD, participates in the acute stage of the inflammatory and pain response, whereas B1 receptors (B1R), through which desArg9BK and desArg10KD act, partake in the chronic stage. We hypothesized that kinins autoregulate B2R and B1R expression in favor of B1R. Incubation of IMR-90 cells with BK (100 nM) led to a loss (89%) of B2R with a half-life (T(1/2)) of 7.0 min. Concomitantly, BK increased B1R (2- to 3-fold) with a T(1/2) of 120 min. DesArg10KD (100 nM)... (More)

Elevated formation of bradykinin (BK) and Lys-BK or kallidin (KD) and their carboxypeptidase metabolites desArg9BK and desArg10KD is evident at sites of inflammation. Moreover, B2 receptors (B2R) which mediate the action of BK and KD, participates in the acute stage of the inflammatory and pain response, whereas B1 receptors (B1R), through which desArg9BK and desArg10KD act, partake in the chronic stage. We hypothesized that kinins autoregulate B2R and B1R expression in favor of B1R. Incubation of IMR-90 cells with BK (100 nM) led to a loss (89%) of B2R with a half-life (T(1/2)) of 7.0 min. Concomitantly, BK increased B1R (2- to 3-fold) with a T(1/2) of 120 min. DesArg10KD (100 nM) had no effect on B2R but increased B1R (3- to 4-fold) with the same rate as BK. Interleukin-1β (IL-1β; 500 pg/ml) also increased B1R (4- to 6-fold). Although both desArg10KD and BK increased the leve of L-1β mRNA, IL-1β receptor antagonist inhibited the increase in B1R only in response to BK. DesArg10KD and BK synergistically increased B1R (9- fold), which was further increased by inclusion of IL-1β (36-fold). Therefore, kinin metabolism and kinin-stimulated production of cytokines may play a pivotal role in shifting the repertoire of kinin receptor subtypes n favor of B1R during inflammation.

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author
; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Pharmacology
volume
56
issue
2
pages
325 - 333
publisher
American Society for Pharmacology and Experimental Therapeutics
external identifiers
  • scopus:0032794136
  • pmid:10419551
ISSN
0026-895X
DOI
10.1124/mol.56.2.325
language
English
LU publication?
no
id
414e2e66-3d69-4e62-8708-8b5c4561a76d
date added to LUP
2019-06-10 11:06:34
date last changed
2024-01-30 22:45:27
@article{414e2e66-3d69-4e62-8708-8b5c4561a76d,
  abstract     = {{<p>Elevated formation of bradykinin (BK) and Lys-BK or kallidin (KD) and their carboxypeptidase metabolites desArg<sup>9</sup>BK and desArg<sup>10</sup>KD is evident at sites of inflammation. Moreover, B2 receptors (B2R) which mediate the action of BK and KD, participates in the acute stage of the inflammatory and pain response, whereas B1 receptors (B1R), through which desArg<sup>9</sup>BK and desArg<sup>10</sup>KD act, partake in the chronic stage. We hypothesized that kinins autoregulate B2R and B1R expression in favor of B1R. Incubation of IMR-90 cells with BK (100 nM) led to a loss (89%) of B2R with a half-life (T(1/2)) of 7.0 min. Concomitantly, BK increased B1R (2- to 3-fold) with a T(1/2) of 120 min. DesArg<sup>10</sup>KD (100 nM) had no effect on B2R but increased B1R (3- to 4-fold) with the same rate as BK. Interleukin-1β (IL-1β; 500 pg/ml) also increased B1R (4- to 6-fold). Although both desArg<sup>10</sup>KD and BK increased the leve of L-1β mRNA, IL-1β receptor antagonist inhibited the increase in B1R only in response to BK. DesArg<sup>10</sup>KD and BK synergistically increased B1R (9- fold), which was further increased by inclusion of IL-1β (36-fold). Therefore, kinin metabolism and kinin-stimulated production of cytokines may play a pivotal role in shifting the repertoire of kinin receptor subtypes n favor of B1R during inflammation.</p>}},
  author       = {{Phagoo, Stephen B. and Poole, Stephen and Leeb-Lundberg, L. M.Fredrik}},
  issn         = {{0026-895X}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{325--333}},
  publisher    = {{American Society for Pharmacology and Experimental Therapeutics}},
  series       = {{Molecular Pharmacology}},
  title        = {{Autoregulation of bradykinin receptors : Agonists in the presence of interleukin-1β shift the repertoire of receptor subtypes from B2 to B1 in human lung fibroblasts}},
  url          = {{http://dx.doi.org/10.1124/mol.56.2.325}},
  doi          = {{10.1124/mol.56.2.325}},
  volume       = {{56}},
  year         = {{1999}},
}