Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor

Biochem Biophys Res Commun. 1998 Oct 20;251(2):471-6. doi: 10.1006/bbrc.1998.9489.


In the search for an endogenous ligand of the orphan G protein-coupled receptor APJ, the presence of the ligand in various tissue extracts was examined by measuring the increase in extracellular acidification rate of the cells expressing the APJ receptor as a specific signal induced by the interaction of the receptor and ligand. By monitoring this activity, we isolated an APJ receptor ligand, designated apelin, from bovine stomach extracts. The structures of bovine and human apelin preproproteins were deduced from the sequences of the corresponding cDNAs. The preproproteins consisted of 77 amino acid residues, and the apelin sequence was encoded in the C-terminal regions. Synthetic peptides derived from the C-terminal amino acid sequence of bovine preproapelin were capable of specifically promoting the acidification rate in the cells expressing the APJ receptor in a range from 10(-7) to 10(-10) M, indicating that apelin is an endogenous ligand for the APJ receptor.

MeSH terms

  • Amino Acid Sequence
  • Amygdala / metabolism
  • Animals
  • Apelin
  • Apelin Receptors
  • Base Sequence
  • CHO Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cattle
  • Cloning, Molecular
  • Cricetinae
  • GTP-Binding Proteins / metabolism
  • Gastric Mucosa / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Lung / metabolism
  • Molecular Sequence Data
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Polymerase Chain Reaction
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, G-Protein-Coupled*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tissue Extracts / chemistry
  • Tissue Extracts / metabolism
  • Transfection


  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Dopamine D2
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • Tissue Extracts
  • GTP-Binding Proteins