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Extracellular calcium-sensing receptor is functionally expressed in human artery

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Molostvov, Guerman, James, Sean G., Fletcher, Simon, Bennett, Jeanette, Lehnert, Hendrik, Bland, Rosemary and Zehnder, Daniel (2007) Extracellular calcium-sensing receptor is functionally expressed in human artery. American Journal of Physiology: Renal Physiology, Vol.293 (No.3). F946-F955. doi:10.1152/ajprenal.00474.2006

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Official URL: http://dx.doi.org/10.1152/ajprenal.00474.2006

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Abstract

Extracellular calcium-sensing receptor is functionally expressed in human artery. Am J Physiol Renal Physiol 293: F946-F955, 2007. First published May 30, 2007; doi:10.1152/ajprenal.00474.2006.- Accelerated medial calcification is a major cause of premature cardiovascular mortality in patients with chronic kidney disease (CKD). Evidence suggests that extracellular concentration of Ca-2 (+) and vascular smooth muscle cells may play a pivotal role in the pathogenesis of vascular calcification. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor that is expressed in a range of tissues, but characterization of its expression and function in the cardiovascular system is limited. Here we report the expression of CaSR mRNA (RT-PCR) and protein ( Western blotting and immunocytochemistry) in human aortic smooth muscle cells (HAoSMC). Treatment of HAoSMC with Ca2 (+) (0-5 mM; 0-30 min) or the CaSR agonists gentamycin and neomycin ( 0-300 mu M; 0-30 min) resulted in a dose- and time-dependent phosphorylation of ERK1/2. Gentamycin- and neomycin-mediated ERK1/2 stimulation was inhibited by pretreatment with PD-98059, an ERK-activating kinase 1 (MEK1) inhibitor, confirming specificity of the observed effects. ERK1/2 activation was inhibited in HAoSMC, with CaSR expression knocked down by transfection with specific small-interference RNA, which confirmed that the observed neomycin/gentamycininduced MEK1/ERK1/2 activation was mediated via the CaSR. CaSR mRNA and protein were also expressed in large and small arteries from normal subjects ( kidney donors) and patients with end-stage renal disease ( ESRD). The CaSR was detected in smooth muscle and endothelial cells. Expression was significantly lower in arteries from ESRD patients. In conclusion, these data not only demonstrate the presence of a functional CaSR in human artery but show a correlation between CaSR expression and progression of CKD.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: American Journal of Physiology: Renal Physiology
Publisher: American Physiological Society
ISSN: 0363-6127
Official Date: September 2007
Dates:
DateEvent
September 2007Published
Volume: Vol.293
Number: No.3
Number of Pages: 10
Page Range: F946-F955
DOI: 10.1152/ajprenal.00474.2006
Status: Not Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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