Send to

Choose Destination
See comment in PubMed Commons below
Endocrinology. 2005 Jan;146(1):231-6. Epub 2004 Oct 14.

Modification of the terminal residue of apelin-13 antagonizes its hypotensive action.

Author information

Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.


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.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Support Center