α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

Aim：It is unclear why α1D-adrenergic receptors （α1D-ARs） play a critical role in the mediation of peripheral vascular resistance and blood pressure in situ but function inefficiently when studied in vitro. The present study examined the causes for these inconsistencies in native α1-adrenergic functi...

Full description

Saved in:
Bibliographic Details
Published in:Acta pharmacologica Sinica 2009-12, Vol.30 (12), p.1585-1593
Main Authors: Fan, Lin-lin, Ren, Shuang, Zhou, Hong, Wang, Ying, Xu, Ping-xiang, He, Jun-qi, Luo, Da-li
Format: Article
Language:English
Subjects:
Original
人工鱼礁
受体亚型
心肌细胞培养
敏感性
细胞收缩
肾上腺素受体
蛋白表达
血管平滑肌细胞
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aim：It is unclear why α1D-adrenergic receptors （α1D-ARs） play a critical role in the mediation of peripheral vascular resistance and blood pressure in situ but function inefficiently when studied in vitro. The present study examined the causes for these inconsistencies in native α1-adrenergic functional performance between the vascular smooth muscle and myocytes. Methods： The α1-adrenergic mediated contraction, Ca^2＋ signaling and the subcellular receptor distribution were evaluated using the Fluo-4, BODIPY-FL prazosin and subtype-specific antibodies. Results： Rat aortic rings and freshly dissociated myocytes displayed contractile and increased intracellular Ca^2＋ responses to stimula- tion with phenylephrine （PE, 10 μmol）, respectively. However, the PE-induced responses disappeared completely in cultured aortic myocytes, whereas PE-enhanced Ca^2＋ transients were seen in cultured rat cardiac myocytes. Further studies indicated that α1D-ARs, the major receptor subtype responsible for the α1-adrenergic regulation of aortic contraction, were distributed both intracellularly and at the cell membrane in freshly dispersed aortic myocytes, similar to the α1A-AR subcellular localization in the cultured cardiomyocytes. In the cultured aortic myocytes, however, in addition to a marked decrease in their protein expression relative to the aorta, most labeling signals for α1D-ARs were found in the cytoplasm. Importantly, treating the culture medium with charcoal/dextran caused the reappearance of α1D-ARs at the cell surface and a partial restoration of the Ca^2＋ signal response to PE in approximately 30% of the cultured cells. Conclusion： Reduction in （α1D-AR total protein expression and disappearance from the cell surface contribute to the insensitivity of cultured vascular smooth muscle cells to α1-adrenergic receptor activation.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2009.160