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Gangliosides and chondroitin sulfate desensitize and internalize B2 bradykinin receptors.

Abstract：

:Prolonged or repeated agonist activation of G-protein-coupled receptors (GPCRs) initiates their desensitization and internalization, rendering them unresponsive to agonist activation. We analyzed how gangliosides and chondroitin sulfate affect B2 bradykinin (BK) receptors (B2Rs). Gangliosides and chondroitin sulfate did not stimulate intracellular Ca(2+) release from B2R-expressing CHO-K1 cells, but repeated exposure desensitized B2Rs to BK stimulation. Microscopic observation of DsRed-fused B2Rs revealed that several gangliosides and chondroitin sulfate C (CSC) effectively internalized B2Rs. Ganglioside-CSC treatment of B2R mutant-expressing cells failed to desensitize and internalize the mutant receptors. As this mutant lacks the first extracellular domain and cannot activate GPCR kinase (GRK), gangliosides and CSC likely initiate B2R desensitization and endocytosis through GRK-mediated B2R phosphorylation.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Shimazaki A,Nakagawa T,Mitoma J,Higashi H

doi

10.1016/j.bbrc.2012.02.142

subject

Has Abstract

pub_date

2012-03-30 00:00:00

pages

193-8

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)00401-9

journal_volume

420

pub_type

杂志文章

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