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

In English

Författare

Summary, in English

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.

Avdelning/ar

  • Drug Target Discovery

Publiceringsår

2007

Språk

Engelska

Sidor

494-507

Publikation/Tidskrift/Serie

Molecular Pharmacology

Volym

71

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Pharmacology and Experimental Therapeutics

Ämne

  • Pharmacology and Toxicology

Status

Published

Forskningsgrupp

  • Drug Target Discovery

ISBN/ISSN/Övrigt

  • ISSN: 1521-0111