Kinins promote B2 receptor endocytosis and delay constitutive B1 receptor endocytosis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/163182
- author
- Enquist, Johan LU ; Skröder, Carl LU ; Whistler, Jennifer L and Leeb-Lundberg, Fredrik LU
- organization
- publishing date
- 2007
- 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
- 2016-04-01 11:59:32
- date last changed
- 2022-04-13 04:26:42
@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}},
doi = {{10.1124/mol.106.030858}},
volume = {{71}},
year = {{2007}},
}