Document Detail


Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart.
MedLine Citation:
PMID:  20833954     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
As a G protein-coupled receptor, the extracellular Ca(2+)-sensing receptor (CaSR) responds to changes not only in extracellular Ca(2+), but also to many other ligands. CaSR has been found to be expressed in the hearts and cardiovascular system. In this study, we confirmed that CaSR is expressed in mouse cardiomyocytes and showed that it is predominantly localized in caveolae. The goal of this study was to investigate whether CaSR plays a cardioprotective role in ischemic preconditioning (IPC). Hearts from C57BL/6J mice (male, 12-16 wk) were perfused in the Langendorff mode and subjected to the following treatments: 1) control perfusion; 2) perfusion with a specific CaSR antagonist, NPS2143; 3) IPC (four cycles of 5 min of global ischemia and 5 min of reperfusion); or 4) perfusion with NPS2143 before and during IPC. Following these treatments, hearts were subjected to 20 min of no-flow global ischemia and 120 min of reperfusion. Compared with control, IPC significantly improved postischemic left ventricular functional recovery and reduced infarct size. Although NPS2143 perfusion alone did not change the hemodynamic function and did not change the extent of postischemic injury, NPS2143 treatment abolished cardioprotection of IPC. Through immunoblot analysis, it was demonstrated that IPC significantly increased the levels of phosphorylated ERK1/2, AKT, and GSK-3β, which were also prevented by NPS2143 treatment. Taken together, the distribution of CaSR in caveolae along with NPS2143-blockade of IPC-induced cardioprotective signaling suggest that the activation of CaSR during IPC is cardioprotective by a process involving caveolae.
Authors:
Junhui Sun; Elizabeth Murphy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2010-09-10
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-11-29     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1309-17     Citation Subset:  IM    
Affiliation:
Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bldg 10/Rm 8N206, Bethesda, MD 20892,USA. sun1@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Caveolin 3 / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
Glycogen Synthase Kinase 3 / metabolism
Ischemic Preconditioning, Myocardial*
Male
Mice
Mice, Inbred C57BL
Models, Animal
Myocardial Reperfusion Injury / metabolism*,  prevention & control*
Myocytes, Cardiac / drug effects,  metabolism*
Naphthalenes / pharmacology
Parathyroid Hormone-Related Protein / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Calcium-Sensing / antagonists & inhibitors,  metabolism*
Signal Transduction / physiology
Ventricular Function, Left / physiology
Chemical
Reg. No./Substance:
0/Cav3 protein, mouse; 0/Caveolin 3; 0/N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; 0/Naphthalenes; 0/Parathyroid Hormone-Related Protein; 0/Receptors, Calcium-Sensing; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections
Comment In:
Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1300-1   [PMID:  20852055 ]

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