[(125)I]-(Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man

Br J Pharmacol. 2001 Mar;132(6):1255-60. doi: 10.1038/sj.bjp.0703939.


1. We have determined the binding characteristics of [(125)I]-(Pyr(1))Apelin-13, a putative ligand for the APJ orphan receptor in human cardiovascular and rat tissue and investigated the functional properties of (Pyr(1))Apelin-13 in human saphenous vein. 2. The binding of [(125)I]-(Pyr(1))Apelin-13 to sections of human heart tissue was time dependent and rapid at 23 degrees C. Data were fitted to a single site model with an association rate constant (k(obs)) of 0.115 min(-1). [(125)I]-(Pyr(1))Apelin-13 also dissociated from a single site with a dissociation rate constant of 0.0105 min(-1). 3. In saturation binding experiments [(125)I]-(Pyr(1))Apelin-13 bound to human left ventricle with a K(D) value of 0.35+/-0.08 nM, B(max) of 4.3+/-0.9 fmol mg(-1) protein with a Hill slope of 0.97+/-0.04 and to the right atria with a K(D) of 0.33+/-0.09 nM, B(max) of 3.1+/-0.6 fmol mg(-1) protein and a Hill slope of 0.93+/-0.05. 4. [(125)I]-(Pyr(1))Apelin-13 binding sites were localized using autoradiography to human cardiovascular tissue, including coronary artery, aorta and saphenous vein grafts. In rat tissue a high density of receptors were localized to the molecular layer of the rat cerebellum, rat lung, rat heart and low levels in the rat kidney cortex. 2. (Pyr(1))Apelin-13 potently contracted human saphenous vein with a pD(2) value of 8.4+/-0.2 (n=8). The maximum response elicited by the peptide was 22.6+/-6% of 100 mM KCl. 6. We provide the first evidence of APJ receptor expression, relative densities and functional properties of (Pyr(1))Apelin-13 in human cardiovascular tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apelin
  • Apelin Receptors
  • Autoradiography
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Iodine Radioisotopes
  • Middle Aged
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D2 / physiology
  • Receptors, G-Protein-Coupled*
  • Saphenous Vein / drug effects
  • Saphenous Vein / metabolism
  • Vasoconstrictor Agents / metabolism*


  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Apln protein, rat
  • Aplnr protein, rat
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Iodine Radioisotopes
  • Receptors, Dopamine D2
  • Receptors, G-Protein-Coupled
  • Vasoconstrictor Agents