Document Detail


Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in heart failure patients with a loss-of-function polymorphism of the presynaptic alpha2C-adrenergic receptor.
MedLine Citation:
PMID:  14668769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Patients with a deletion of 4 consecutive amino acids in the gene encoding for the alpha(2C)-adrenergic receptor (alpha(2C)Del322-325) have an increased prevalence of clinical heart failure, worse clinical status, and a lower left ventricular ejection fraction compared with patients without this deletion. We postulated that patients with the alpha(2C)Del322-325 polymorphism would have a compensatory increase in norepinephrine uptake-1 transporter activity as measured by iodine 123 metaiodobenzylguanidine (MIBG). METHODS AND RESULTS: Thirty-nine patients with heart failure related to idiopathic dilated cardiomyopathy were studied. Demographic characteristics, left ventricular ejection fraction, maximum oxygen consumption, exercise duration, and plasma norepinephrine levels did not differ between patients with the alpha(2C) receptor polymorphism (n = 9) and those without it (n = 30). Patients with the alpha(2C)Del322-325 polymorphism had significantly greater heart-to-mediastinum ratios of I-123 MIBG at 4 hours after tracer injection (1.60 +/- 0.19 vs 1.41 +/- 0.19, P =.0117) and greater background-corrected heart counts per pixel at 4 hours compared with patients without the polymorphism. CONCLUSIONS: Patients with genetic impairment of the alpha(2C)-adrenergic receptor have augmented activity of the norepinephrine uptake-1 transporter as measured by I-123 MIBG. Further studies are needed to clarify the mechanism by which uptake-1 transporter activity is increased in this setting.
Authors:
Myron C Gerson; Lynne E Wagoner; Nancy McGuire; Stephen B Liggett
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology     Volume:  10     ISSN:  1071-3581     ISO Abbreviation:  J Nucl Cardiol     Publication Date:    2003 Nov-Dec
Date Detail:
Created Date:  2003-12-11     Completed Date:  2004-05-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9423534     Medline TA:  J Nucl Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  583-9     Citation Subset:  IM    
Affiliation:
Division of Cardiology, University of Cincinnati, Ohio 45267-0542, USA. myron.gerson@uc.edu
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MeSH Terms
Descriptor/Qualifier:
3-Iodobenzylguanidine / diagnostic use*
Cardiac Output, Low / complications,  metabolism*,  radionuclide imaging*
Cardiomyopathy, Dilated / complications,  metabolism*,  radionuclide imaging*
Female
Gene Deletion
Genetic Predisposition to Disease / genetics
Heart / innervation,  radionuclide imaging
Heart Failure / complications,  metabolism,  radionuclide imaging
Humans
Male
Middle Aged
Mutation
Norepinephrine Plasma Membrane Transport Proteins
Polymorphism, Genetic / genetics
Radiopharmaceuticals / diagnostic use
Receptors, Adrenergic, alpha-2 / deficiency,  genetics*
Sympathetic Nervous System / radionuclide imaging
Symporters / genetics*,  metabolism*
Ventricular Dysfunction, Left / metabolism*,  radionuclide imaging*
Chemical
Reg. No./Substance:
0/Norepinephrine Plasma Membrane Transport Proteins; 0/Radiopharmaceuticals; 0/Receptors, Adrenergic, alpha-2; 0/SLC6A2 protein, human; 0/Symporters; 0/adrenergic receptor alpha(2C); 77679-27-7/3-Iodobenzylguanidine
Comments/Corrections
Comment In:
J Nucl Cardiol. 2003 Nov-Dec;10(6):700-4   [PMID:  14668785 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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