RGD Reference Report - G protein-coupled receptor kinase (GRK)2 is a key negative regulator of itch: L-glutamine attenuates itch via a rapid induction of GRK2 in an ERK-dependent way. - Rat Genome Database

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G protein-coupled receptor kinase (GRK)2 is a key negative regulator of itch: L-glutamine attenuates itch via a rapid induction of GRK2 in an ERK-dependent way.

Authors: Im, Yu-Na  Lee, Yu-Dong  Park, Jeong-Soo  Kim, Hae-Kyoung  Im, Suhn-Young  Song, Hwa-Ryung  Lee, Hern-Ku  Han, Myung-Kwan 
Citation: Im YN, etal., J Invest Dermatol. 2018 Mar 9. pii: S0022-202X(18)30220-3. doi: 10.1016/j.jid.2018.02.036.
RGD ID: 13513974
Pubmed: PMID:29530536   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jid.2018.02.036   (Journal Full-text)

Many itch mediators activate G-protein coupled receptor (GPCR), and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by G protein-coupled receptor kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the linkage between GRKs and glutamine (Gln), an amino acid previously demonstrated as an itching reliever. Itch responses were evoked by histamine, chloroquine (CQ), and dinitrochlorobenzene (DNCB)-induced contact dermatitis (CD). Phosphorylation and protein expression were detected by immunofluorescent staining and Western blotting. GRK2 knockdown using siRNA enhanced itch responses evoked by histamine, CQ, and DNCB-induced CD, whereas GRK2 overexpression using GRK2 expressing adenovirus reduced the itch responses. Gln reduced all itch evoked by histamine, CQ, and DNCB-induced CD. Gln-mediated inhibition of itch was abolished by GRK2 knockdown. Gln application resulted in a rapid and strong expression GRK2 in not only DNCB-induced CD (within 10 min), but also cultured rat dorsal root ganglion cells, F11 (within 1 min). ERK inhibitor abrogates Gln-mediated GRK2 expression and inhibition of itch in DNCB-induced CD. Our data indicate that GRK2 is a key negative regulator of itch and Gln attenuates itch via a rapid induction of GRK2 in an ERK-dependent way.




  
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Original Reference(s)
GRK2HumanPruritus severityISOGrk2 (Mus musculus) RGD 
Grk2RatPruritus severityISOGrk2 (Mus musculus) RGD 
Grk2MousePruritus severityIMP  RGD 


Genes (Rattus norvegicus)
Grk2  (G protein-coupled receptor kinase 2)

Genes (Mus musculus)
Grk2  (G protein-coupled receptor kinase 2)

Genes (Homo sapiens)
GRK2  (G protein-coupled receptor kinase 2)