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Kinins promote B2 receptor endocytosis and delay constitutive B1 receptor endocytosis.

Enquist, Johan LU ; Skröder, Carl LU ; Whistler, Jennifer L and Leeb-Lundberg, Fredrik LU (2007) In Molecular Pharmacology 71(2). p.494-507
Abstract
Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell surface. B2Rs, which require agonist for activity, are stable plasma membrane components without agonist but recruit beta-arrestin 2, internalize in a clathrin-dependent manner, and recycle rapidly upon agonist treatment. In contrast, B1Rs, which are inducible and constitutively active, constitutively internalize without agonist via a clathrin-dependent pathway, do not recruit beta-arrestin 2, bind G protein-coupled receptor... (More)
Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell surface. B2Rs, which require agonist for activity, are stable plasma membrane components without agonist but recruit beta-arrestin 2, internalize in a clathrin-dependent manner, and recycle rapidly upon agonist treatment. In contrast, B1Rs, which are inducible and constitutively active, constitutively internalize without agonist via a clathrin-dependent pathway, do not recruit beta-arrestin 2, bind G protein-coupled receptor sorting protein, and target lysosomes for degradation. Agonist delays B1R endocytosis, thus transiently stabilizing the receptor. Most of the receptor trafficking phenotypes are transplantable from one receptor to the other through exchange of the C-terminal receptor tails, indicating that the tails contain epitopes that are important for the binding of protein partners that participate in the endocytic and postendocytic receptor choices. It is noteworthy that the agonist delay of B1R endocytosis is not transplanted to the B2R via the B1R tail, suggesting that this property of the B1R requires another domain. These events provide a rapid kinin-dependent mechanism for 1) regulating the constitutive B1R activity and 2) shifting the balance of accessible receptors in favor of B1R. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Pharmacology
volume
71
issue
2
pages
494 - 507
publisher
American Society for Pharmacology and Experimental Therapeutics
external identifiers
  • wos:000243604900012
  • scopus:33846428788
ISSN
1521-0111
DOI
10.1124/mol.106.030858
language
English
LU publication?
yes
id
118a9086-0abd-4c54-bf02-1dd54b05b385 (old id 163182)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17110500&dopt=Abstract
date added to LUP
2007-07-11 16:24:46
date last changed
2017-08-13 03:35:58
@article{118a9086-0abd-4c54-bf02-1dd54b05b385,
  abstract     = {Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell surface. B2Rs, which require agonist for activity, are stable plasma membrane components without agonist but recruit beta-arrestin 2, internalize in a clathrin-dependent manner, and recycle rapidly upon agonist treatment. In contrast, B1Rs, which are inducible and constitutively active, constitutively internalize without agonist via a clathrin-dependent pathway, do not recruit beta-arrestin 2, bind G protein-coupled receptor sorting protein, and target lysosomes for degradation. Agonist delays B1R endocytosis, thus transiently stabilizing the receptor. Most of the receptor trafficking phenotypes are transplantable from one receptor to the other through exchange of the C-terminal receptor tails, indicating that the tails contain epitopes that are important for the binding of protein partners that participate in the endocytic and postendocytic receptor choices. It is noteworthy that the agonist delay of B1R endocytosis is not transplanted to the B2R via the B1R tail, suggesting that this property of the B1R requires another domain. These events provide a rapid kinin-dependent mechanism for 1) regulating the constitutive B1R activity and 2) shifting the balance of accessible receptors in favor of B1R.},
  author       = {Enquist, Johan and Skröder, Carl and Whistler, Jennifer L and Leeb-Lundberg, Fredrik},
  issn         = {1521-0111},
  language     = {eng},
  number       = {2},
  pages        = {494--507},
  publisher    = {American Society for Pharmacology and Experimental Therapeutics},
  series       = {Molecular Pharmacology},
  title        = {Kinins promote B2 receptor endocytosis and delay constitutive B1 receptor endocytosis.},
  url          = {http://dx.doi.org/10.1124/mol.106.030858},
  volume       = {71},
  year         = {2007},
}