Document Detail


Modification of the terminal residue of apelin-13 antagonizes its hypotensive action.
MedLine Citation:
PMID:  15486224     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The apelin peptide is the endogenous ligand for the apelin G protein-coupled receptor. The distribution of the apelin peptides and receptor are widespread in the central nervous system and periphery, with reported roles in the hypothalamic-pituitary-adrenal axis, blood pressure regulation and as one of the most potent positive inotropic substances yet identified. In this report, we show that in native tissues preproapelin exists as a dimer. Dimeric preproapelin was reduced to monomers by dithiothreitol treatment, indicating disulfide linkages. To evaluate the role of the carboxyl-terminal phenylalanine in the hypotensive action of apelin-13, analogs were generated and tested for their role on blood pressure regulation. Injections of apelin-13 and apelin-12 (15 microg/kg) into spontaneously hypertensive rats lowered systolic and diastolic blood pressure to result in decreases of approximately 60% and 15% in mean arterial blood pressure, respectively. Apelin-13(13[D-Phe]) treatment did not differ from apelin-13 in either efficacy or duration of effect, whereas apelin-13(F13A) revealed a loss of function. However, concomitant administration of apelin-13(F13A) (30 microg/kg) blocked hypotensive effects of apelin-13 (15 microg/kg), which revealed that apelin-13(F13A) behaved as an apelin-specific antagonist.
Authors:
Dennis K Lee; Victor R Saldivia; Tuan Nguyen; Regina Cheng; Susan R George; Brian F O'Dowd
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-10-14
Journal Detail:
Title:  Endocrinology     Volume:  146     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-16     Completed Date:  2005-01-18     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  231-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Blood Pressure / drug effects*
COS Cells
Carrier Proteins / antagonists & inhibitors,  chemistry,  drug effects,  genetics*,  metabolism,  pharmacology*
Cells, Cultured
Cercopithecus aethiops
Dimerization
Dithiothreitol / pharmacology
Intercellular Signaling Peptides and Proteins
Mice
Mice, Transgenic
Phenylalanine
Rats
Rats, Inbred SHR
Rats, Wistar
Chemical
Reg. No./Substance:
0/Apln protein, mouse; 0/Apln protein, rat; 0/Carrier Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/apelin-12 peptide; 0/apelin-13 peptide; 3483-12-3/Dithiothreitol; 63-91-2/Phenylalanine

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


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