RGD Reference Report - Modification of the terminal residue of apelin-13 antagonizes its hypotensive action. - Rat Genome Database

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

Authors: Lee, DK  Saldivia, VR  Nguyen, T  Cheng, R  George, SR  O'Dowd, BF 
Citation: Lee DK, etal., Endocrinology. 2005 Jan;146(1):231-6. Epub 2004 Oct 14.
RGD ID: 1576349
Pubmed: PMID:15486224   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2004-0359   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of blood pressure  IDA 1576349 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
identical protein binding  IPIApln (Rattus norvegicus)1576349homodimerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Apln  (apelin)

Objects referenced in this article
Gene ACE2 angiotensin converting enzyme 2 Homo sapiens
Gene Ace2 angiotensin converting enzyme 2 Mus musculus
Gene Ace2 angiotensin converting enzyme 2 Rattus norvegicus

Additional Information