1. International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand
- Author
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Thomas L Williams, David J. Huggins, Petra Sulentic, Janet J. Maguire, Robyn Macrae, Cai Read, Duuamene Nyimanu, Peiran Yang, Robert C. Glen, and Anthony P. Davenport
- Subjects
0301 basic medicine ,Models, Molecular ,GENE POLYMORPHISM ,Protein Conformation ,Peptide Hormones ,RIGHT-VENTRICULAR FUNCTION ,BLOOD-PRESSURE ,Peptide ,Pharmacology ,INHIBITS INSULIN-SECRETION ,Ligands ,Small Molecule Libraries ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Animals ,Humans ,Tissue Distribution ,Pharmacology & Pharmacy ,Amino Acid Sequence ,Peptide sequence ,Apelin receptor ,Orphan receptor ,chemistry.chemical_classification ,Apelin Receptors ,Science & Technology ,THERAPEUTIC TARGET ,Chemistry ,ORPHAN 7-TRANSMEMBRANE RECEPTOR ,IMMUNODEFICIENCY-VIRUS TYPE-1 ,Small molecule ,3. Good health ,Apelin ,IUPHAR Nomenclature Report ,030104 developmental biology ,CORONARY-ARTERY-DISEASE ,HEART-FAILURE ,Molecular Medicine ,1115 Pharmacology and Pharmaceutical Sciences ,Signal transduction ,Life Sciences & Biomedicine ,HUMAN APJ RECEPTOR ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The predicted protein encoded by the APJ gene discovered in 1993 was originally classified as a class A G protein-coupled orphan receptor but was subsequently paired with a novel peptide ligand, apelin-36 in 1998. Substantial research identified a family of shorter peptides activating the apelin receptor, including apelin-17, apelin-13, and [Pyr1]apelin-13, with the latter peptide predominating in human plasma and cardiovascular system. A range of pharmacological tools have been developed, including radiolabeled ligands, analogs with improved plasma stability, peptides, and small molecules including biased agonists and antagonists, leading to the recommendation that the APJ gene be renamed APLNR and encode the apelin receptor protein. Recently, a second endogenous ligand has been identified and called Elabela/Toddler, a 54-amino acid peptide originally identified in the genomes of fish and humans but misclassified as noncoding. This precursor is also able to be cleaved to shorter sequences (32, 21, and 11 amino acids), and all are able to activate the apelin receptor and are blocked by apelin receptor antagonists. This review summarizes the pharmacology of these ligands and the apelin receptor, highlights the emerging physiologic and pathophysiological roles in a number of diseases, and recommends that Elabela/Toddler is a second endogenous peptide ligand of the apelin receptor protein.
- Published
- 2019