QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.098996v1 317/3/1027    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Desai, A. N. Articles by Eikenburg, D. C. Search for Related Content PubMed PubMed Citation Articles by Desai, A. N. Articles by Eikenburg, D. C. Pubmed/NCBI databases Domain Compound via MeSH Substance via MeSH Hazardous Substances DB EPINEPHRINE

CELLULAR AND MOLECULAR

Involvement of G Protein-Coupled Receptor Kinase (GRK) 3 and GRK2 in Down-Regulation of the _2B-Adrenoceptor

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas

Increasing the cellular levels of G protein-coupled receptor kinase (GRK) 2 or GRK3 renders the _2B-adrenoceptor (AR) more sensitive to agonist-induced down-regulation (J Pharmacol Exp Ther 312:767–773, 2005). However, an absolute requirement of GRK3 and GRK2 for _2B-AR down-regulation is controversial. In this study, using NG108 cells (endogenous _2B-AR), we provide strong evidence for a critical role of both GRK3 and GRK2 in down-regulation of the _2B-AR. Pretreatment of NG108 cells with 20 µM epinephrine (EPI) begins down-regulating the _2B-AR by 2 h. The translocation of GRK3 and GRK2 to the membrane peaks at 30 min, decreasing by 1 h. Although these results may implicate GRK3 and GRK2 in _2B-AR down-regulation, significant receptor down-regulation is not observed until 2 h, after GRK3 and GRK2 translocation has peaked and is declining. To more directly establish a role for GRK3 and GRK2 in _2B-AR down-regulation, NG108 cells were transfected to express GRK3ct, which binds to liberated G subunits, preventing GRK3 and GRK2 translocation to the membrane. Overexpression of GRK3ct prevented not only the translocation of GRK3 and GRK2 but also the down-regulation of the _2B-AR caused by 24-h pretreatment with 20 µM EPI. Taken together, these data provide direct evidence for a role of GRK3 and GRK2 in the down-regulation of the _2B-AR and contribute significantly to the increasing evidence in the literature for a pivotal role of GRKs in modulating the agonist-induced down-regulation of the ₂-AR.

Address correspondence to: Douglas C. Eikenburg, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204. E-mail: deikenburg{at}uh.edu

This article has been cited by other articles:

				S. Salim, K. M. Standifer, and D. C. Eikenburg Extracellular Signal-Regulated Kinase 1/2-Mediated Transcriptional Regulation of G-Protein-Coupled Receptor Kinase 3 Expression in Neuronal Cells J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 51 - 59. [Abstract] [Full Text] [PDF]