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(s)
Type
Journal Article
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.
Date Issued
2019-10-01
Date Acceptance
2019-09-01
Citation
Pharmacological Reviews, 2019, 71 (4), pp.467-502
ISSN
0031-6997
Publisher
American Society for Pharmacology and Experimental Therapeutics
Start Page
467
End Page
502
Journal / Book Title
Pharmacological Reviews
Volume
71
Issue
4
Copyright Statement
© 2019 by The Author(s)
This is an open access article distributed under the CC BY Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/).
This is an open access article distributed under the CC BY Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000500540700002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
ORPHAN 7-TRANSMEMBRANE RECEPTOR
IMMUNODEFICIENCY-VIRUS TYPE-1
CORONARY-ARTERY-DISEASE
INHIBITS INSULIN-SECRETION
RIGHT-VENTRICULAR FUNCTION
HUMAN APJ RECEPTOR
THERAPEUTIC TARGET
BLOOD-PRESSURE
HEART-FAILURE
GENE POLYMORPHISM
Publication Status
Published
Date Publish Online
2019-09-06