Pharmacological reviews, 2015-04, Vol.67 (2), p.389-440
2015
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- Autor(en) / Beteiligte
- Titel
- International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides
- Ist Teil von
- Pharmacological reviews, 2015-04, Vol.67 (2), p.389-440
- Ort / Verlag
- United States: The American Society for Pharmacology and Experimental Therapeutics
- Erscheinungsjahr
- 2015
- Quelle
- Elektronische Zeitschriftenbibliothek - Freely accessible e-journals
- Beschreibungen/Notizen
- Relaxin, insulin-like peptide 3 (INSL3), relaxin-3, and INSL5 are the cognate ligands for the relaxin family peptide (RXFP) receptors 1-4, respectively. RXFP1 activates pleiotropic signaling pathways including the signalosome protein complex that facilitates high-sensitivity signaling; coupling to Gα(s), Gα(i), and Gα(o) proteins; interaction with glucocorticoid receptors; and the formation of hetero-oligomers with distinctive pharmacological properties. In addition to relaxin-related ligands, RXFP1 is activated by Clq-tumor necrosis factor-related protein 8 and by small-molecular-weight agonists, such as ML290 [2-isopropoxy-N-(2-(3-(trifluoromethylsulfonyl)phenylcarbamoyl)phenyl)benzamide], that act allosterically. RXFP2 activates only the Gα(s)- and Gα(o)-coupled pathways. Relaxin-3 is primarily a neuropeptide, and its cognate receptor RXFP3 is a target for the treatment of depression, anxiety, and autism. A variety of peptide agonists, antagonists, biased agonists, and an allosteric modulator target RXFP3. Both RXFP3 and the related RXFP4 couple to Gα(i)/Gα(o) proteins. INSL5 has the properties of an incretin; it is secreted from the gut and is orexigenic. The expression of RXFP4 in gut, adipose tissue, and β-islets together with compromised glucose tolerance in INSL5 or RXFP4 knockout mice suggests a metabolic role. This review focuses on the many advances in our understanding of RXFP receptors in the last 5 years, their signal transduction mechanisms, the development of novel compounds that target RXFP1-4, the challenges facing the field, and current prospects for new therapeutics.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0031-6997eISSN: 1521-0081DOI: 10.1124/pr.114.009472Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4394689
- Format
- –
- Schlagworte
- Allosteric Regulation, Animals, Cell Membrane - enzymology, Cell Membrane - metabolism, Cyclic AMP - physiology, Humans, International Agencies, IUPHAR Nomenclature Reports, Ligands, Models, Molecular, Pharmacology - trends, Pharmacology, Clinical - trends, Protein Isoforms - agonists, Protein Isoforms - chemistry, Protein Isoforms - classification, Protein Isoforms - metabolism, Receptors, G-Protein-Coupled - agonists, Receptors, G-Protein-Coupled - chemistry, Receptors, G-Protein-Coupled - classification, Receptors, G-Protein-Coupled - metabolism, Receptors, Peptide - agonists, Receptors, Peptide - chemistry, Receptors, Peptide - classification, Receptors, Peptide - metabolism, Relaxin - agonists, Relaxin - analogs & derivatives, Relaxin - antagonists & inhibitors, Relaxin - metabolism, Second Messenger Systems, Societies, Scientific, Terminology as Topic