Impaired desensitization of a human polymorphic α2B-adrenergic receptor variant enhances its sympatho-inhibitory activity in chromaffin cells

Cell Communication and Signaling

Research

Anastasios Lymperopoulos¹  Kristy Nguyen¹  Theodoros Kassimatis² 

[1] Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 33328, Fort Lauderdale, FL, USA;Nephrology Department, Asklipieio General Hospital, Athens, Greece;

关键词: PC12 Cell;    Chromaffin Cell;    Catecholamine Secretion;    Adrenal Chromaffin Cell;    Oxymetazoline;   

DOI  :  10.1186/1478-811X-9-5

 received in 2010-12-15, accepted in 2011-02-07,  发布年份 2011

来源: Springer

【 摘 要 】

Backgroundα2-adrenergic receptors (ARs) mediate many cellular actions of epinephrine and norepinephrine and inhibit their secretion from adrenal chromaffin cells. Like many other G-protein coupled receptors (GPCRs), they undergo agonist-dependent phopshorylation and desensitization by GPCR Kinases (GRKs), a phenomenon recently shown to play a major role in the sympathetic overdrive that accompanies and aggravates chronic heart failure. A deletion polymorphism in the human α2B-AR gene (Glu301-303) causes impaired agonist-promoted receptor phosphorylation and desensitization in heterologous cell lines. Given the importance of α2-ARs in regulation of catecholamine secretion from chromaffin cells, we sought to investigate, in the present study, the desensitization properties and the sympatho-inhibitory activity of this variant in a chromaffin cell line. For this purpose, we expressed this variant and its wild type counterpart in the well-established chromaffin cell line PC12, and performed receptor phosphorylation and desensitization studies, as well as in vitro catecholamine secretion assays.ResultsBoth the agonist-induced phosphorylation and agonist-dependent desensitization of the human Glu301-303 deletion polymorphic α2B-AR are significantly impaired in PC12 cells, resulting in enhanced signaling to inhibition of cholinergic-induced catecholamine secretion in vitro.ConclusionThis α2B-AR gene polymorphism (Glu301-303 deletion) might confer better protection against conditions characterized and aggravated by sympathetic/catecholaminergic overstimulation in vivo.

【 授权许可】

Unknown   
© Nguyen et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.