The apelin receptor responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) by a so far unidentified enzymatic pathway . A second family of peptides discovered independently and named Elabela  or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [3,4]. Structure-activity relationship Elabela analogues have been described .
Chng SC, Ho L, Tian J, et al. ELABELA: a hormone essential for heart development signals via the apelin receptor. Dev Cell 2013;27:672-80.
Yang P, Read C, Kuc RE, et al. Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension. Circulation 2017;135:1160-1173.
Pauli A, Norris ML, Valen E, et al. Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 2014;343:1248636.
Murza A, Sainsily X, Coquerel D, et al. Discovery and Structure-Activity Relationship of a Bioactive Fragment of ELABELA that Modulates Vascular and Cardiac Functions. J Med Chem 2016;59:2962-72.
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