Gangliosides and chondroitin sulfate desensitize and internalize B2 bradykinin receptors

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• 作者：Ayaka Shimazaki ; Tetsuto Nakagawa ; Junya Mitoma ; Hideyoshi Higashi ; ^{hhigashi@tohoku-pharm.ac.jp}
• 关键词：BK ; bradykinin ; B2R ; B2 bradykinin receptor ; CSC ; chondroitin sulfate C ; CSE ; chondroitin sulfate E ; GRK ; G-protein-coupled receptor kinase ; GM1 ; Gal¦Â3GalNAc¦Â4(Neu5Ac¦Á3)Gal¦Â4GlcCer ; GD1a ; Neu5Ac¦Á3Gal¦Â3GalNAc¦Â4(Neu5Ac¦Á3)Gal¦Â4GlcCer ; GD1b ; Gal¦Â3Ga
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：30 March, 2012
• 年：2012
• 卷：420
• 期：1
• 页码：193-198
• 全文大小：692 K

文摘

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 Ca²⁺ 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.