Document Detail


Atrial natriuretic peptide is eliminated from the brain by natriuretic peptide receptor-C-mediated brain-to-blood efflux transport at the blood-brain barrier.
MedLine Citation:
PMID:  20628403     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cerebral atrial natriuretic peptide (ANP), which is generated in the brain, has functions in the regulation of brain water and electrolyte balance, blood pressure and local cerebral blood flow, as well as in neuroendocrine functions. However, cerebral ANP clearance is still poorly understood. The purpose of this study was to clarify the mechanism of blood-brain barrier (BBB) efflux transport of ANP in mouse. Western blot analysis showed expression of natriuretic peptide receptor (Npr)-A and Npr-C in mouse brain capillaries. The brain efflux index (BEI) method confirmed elimination of [(125)I]human ANP (hANP) from mouse brain across the BBB. Inhibition studies suggested the involvement of Npr-C in vivo. Furthermore, rapid internalization of [(125)I]hANP by TM-BBB4 cells (an in vitro BBB model) was significantly inhibited by Npr-C inhibitors and by two different Npr-C-targeted short interfering RNAs (siRNAs). Finally, treatment with 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) significantly increased Npr-C expression in TM-BBB4 cells, as determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted absolute proteomics. Our results indicate that Npr-C mediates brain-to-blood efflux transport of ANP at the mouse BBB as a pathway of cerebral ANP clearance. It seems likely that levels of natriuretic peptides in the brain are modulated by 1,25(OH)(2)D(3) through upregulation of Npr-C expression at the BBB.
Authors:
Shingo Ito; Sumio Ohtsuki; Yuki Katsukura; Miho Funaki; Yusuke Koitabashi; Akihiko Sugino; Sho Murata; Tetsuya Terasaki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-14
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  31     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-04     Completed Date:  2011-03-17     Revised Date:  2012-02-01    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  457-66     Citation Subset:  IM    
Affiliation:
Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Atrial Natriuretic Factor / metabolism*
Blood-Brain Barrier / physiology*
Blotting, Western
Brain Chemistry / drug effects*
Calcitriol / pharmacology
Calcium Channel Agonists / pharmacology
Capillaries / metabolism
Cell Line
Chromatography, High Pressure Liquid
Endothelial Cells / metabolism
Humans
Iodine Radioisotopes / diagnostic use
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Natriuretic Peptide, C-Type / biosynthesis*
RNA, Small Interfering / genetics
Receptors, Atrial Natriuretic Factor / biosynthesis,  physiology*
Reverse Transcriptase Polymerase Chain Reaction
Tandem Mass Spectrometry
Transfection
Chemical
Reg. No./Substance:
0/Calcium Channel Agonists; 0/Iodine Radioisotopes; 0/RNA, Small Interfering; 127869-51-6/Natriuretic Peptide, C-Type; 32222-06-3/Calcitriol; 85637-73-6/Atrial Natriuretic Factor; EC 4.6.1.2/Receptors, Atrial Natriuretic Factor; EC 4.6.1.2/atrial natriuretic factor receptor A; EC 4.6.1.2/atrial natriuretic factor receptor C

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


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