Investigation of the role of βarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus

Neuropharmacology
Jenny MorgenweckLaura M Bohn

Abstract

The kappa opioid receptor (KOR) is involved in mediating pruritus; agonists targeting this receptor have been used to treat chronic intractable itch. Conversely, antagonists induce an itch response at the site of injection. As a G protein-coupled receptor (GPCR), the KOR has potential for signaling via G proteins and βarrestins, however, it is not clear which of these pathways are involved in the KOR modulation of itch. In this study asked whether the actions of KOR in pruritus involve βarrestins by using βarrestin2 knockout (βarr2-KO) mice as well as a recently described biased KOR agonist that biases receptor signaling toward G protein pathways over βarrestin2 recruitment. We find that the KOR antagonists nor-binaltorphimine (NorBNI) and 5'-guanidinonaltrindole (5'GNTI) induce acute pruritus in C57BL/6J mice, with reduced effects in KOR-KO mice. βArr2-KO mice display less of a response to KOR antagonist-induced itch compared to wild types, however no genotype differences are observed from chloroquine phosphate (CP)-induced itch, suggesting that the antagonists may utilize a KOR-βarrestin2 dependent mechanism. The KOR agonist U50,488H was equally effective in both WT and βarr2-KO mice in suppressing CP-induced itch. Furthermor...Continue Reading

References

Aug 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·S K SharmaM Nirenberg
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·R A NorthM J Christie
Jan 1, 1988·Annals of the New York Academy of Sciences·D E Gmerek, A Cowan
Mar 21, 1998·Chemical & Pharmaceutical Bulletin·H NagaseT Endo
Feb 1, 2002·European Journal of Pharmacology·Yuko TogashiHiroshi Nagase
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·M C Holden KoNorah N Naughton
Oct 13, 2004·European Journal of Pharmacology·Saadet Inan, Alan Cowan
Oct 28, 2005·Journal of the American Society of Nephrology : JASN·Björn WikströmYuji Ueno
May 2, 2006·The Journal of Biological Chemistry·Michael R BruchasCharles Chavkin
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael R BruchasCharles Chavkin
Oct 10, 2008·The Journal of Pharmacology and Experimental Therapeutics·Mei-Chuan Ko, Stephen M Husbands
Nov 21, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Hiroo KumagaiHiromichi Suzuki
Apr 20, 2010·Psychopharmacology·Michael R Bruchas, Charles Chavkin
Dec 29, 2010·Indian Journal of Pharmaceutical Sciences·S E AghahowaI M Arhewoh
Jun 28, 2012·The Journal of Biological Chemistry·Marie-Laure RivesJonathan A Javitch
Aug 8, 2012·American Journal of Nephrology·Hiroo KumagaiHiromichi Suzuki
Dec 12, 2012·Molecular Pain·Fiona E HolmesDavid Wynick
Jun 19, 2013·The Journal of Biological Chemistry·Cullen L SchmidLaura M Bohn
Sep 18, 2013·International Journal of Clinical Pharmacology and Therapeutics·Yuji UenoTomoji Yanagita
Oct 12, 2013·Molecular Pharmacology·Kate L WhiteBryan L Roth
Nov 5, 2013·The Journal of Biological Chemistry·Lei ZhouLaura M Bohn
Apr 1, 2014·Current Opinion in Cell Biology·Lei Zhou, Laura M Bohn
Aug 15, 2014·Journal of Neurophysiology·Tasuku AkiyamaE Carstens
Oct 17, 2014·The Journal of Pharmacology and Experimental Therapeutics·Kate L WhiteBryan L Roth

❮ Previous
Next ❯

Citations

Feb 3, 2016·Trends in Pharmacological Sciences·Michael R Bruchas, Bryan L Roth
May 11, 2016·Proceedings of the National Academy of Sciences of the United States of America·Achla GuptaLakshmi A Devi
Nov 5, 2016·Neuropharmacology·Santhanalakshmi SundaramurthySammanda Ramamoorthy
Oct 19, 2017·Nature Chemical Biology·Bryan L RothBrian K Shoichet
Jun 23, 2018·Science·Jeffrey J LiuMatthias Mann
Aug 8, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeffrey J LiuLee-Yuan Liu-Chen
Jun 13, 2017·Experimental Dermatology·Gema TarrasónNúria Godessart
May 7, 2019·Frontiers in Pharmacology·Kendall L MoresRichard M van Rijn
Mar 27, 2020·Frontiers in Pharmacology·Andrea BediniSanti Spampinato
Aug 28, 2020·Canadian Journal of Physiology and Pharmacology·Pierre E Thibeault, Rithwik Ramachandran
Mar 24, 2021·Annual Review of Biochemistry·Tao Che, Bryan L Roth

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.