alexa Agonist Binding and Desensitization of the μ-Opioid Receptor Is Modulated by Phosphorylation of the C-Terminal Tail Domain.
Pathology

Pathology

Journal of Clinical & Experimental Pathology

Author(s): Birdsong WT, Arttamangkul S, Bunzow JR, Williams JT

Abstract Share this page

Abstract Sustained activation of G protein-coupled receptors can lead to a rapid decline in signaling through acute receptor desensitization. In the case of the μ-opioid receptor (MOPr), this desensitization may play a role in the development of analgesic tolerance. It is understood that phosphorylation of MOPr promotes association with β-arrestin proteins, which then facilitates desensitization and receptor internalization. Agonists that induce acute desensitization have been shown to induce a noncanonical high-affinity agonist binding state in MOPr, conferring a persistent memory of prior receptor activation. In the current study, live-cell confocal imaging was used to investigate the role of receptor phosphorylation in agonist binding to MOPr. A phosphorylation cluster in the C-terminal tail of MOPr was identified as a mediator of agonist-induced affinity changes in MOPr. This site is unique from the primary phosphorylation cluster responsible for β-arrestin binding and internalization. Electrophysiologic measurements of receptor function suggest that both phosphorylation clusters may play a parallel role during acute receptor desensitization. Desensitization was unaffected by alanine mutation of either phosphorylation cluster, but was largely eliminated when both clusters were mutated. Overall, this work suggests that there are multiple effects of MOPr phosphorylation that appear to regulate MOPr function: one affecting β-arrestin binding and a second affecting agonist binding. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
This article was published in Mol Pharmacol and referenced in Journal of Clinical & Experimental Pathology

Relevant Expert PPTs

Relevant Speaker PPTs

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

agriaquaculture@omicsonline.com

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

biochemjournals@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

chemistryjournals@omicsonline.com

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

clinicaljournals@omicsonline.com

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

engineeringjournals@omicsonline.com

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

nutritionjournals@omicsonline.com

1-702-714-7001Extn: 9042

General Science

Andrea Jason

generalscience@omicsonline.com

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

geneticsmolbio@omicsonline.com

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immunomicrobiol@omicsonline.com

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

nursinghealthcare@omicsonline.com

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

medicaljournals@omicsonline.com

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuropsychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

pharmajournals@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords