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10.1124/pr.114.009472

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suck abstract from ncbi


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pmid25761609
      Pharmacol+Rev 2015 ; 67 (2 ): 389-440
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  • 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 #MMPMID25761609
  • Halls ML ; Bathgate RA ; Sutton SW ; Dschietzig TB ; Summers RJ
  • Pharmacol Rev 2015[]; 67 (2 ): 389-440 PMID25761609 show ga
  • 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 G?(s), G?(i), and G?(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 G?(s)- and G?(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 G?(i)/G?(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 ?-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.
  • |*Models, Molecular [MESH]
  • |*Second Messenger Systems [MESH]
  • |Allosteric Regulation [MESH]
  • |Animals [MESH]
  • |Cell Membrane/enzymology/metabolism [MESH]
  • |Cyclic AMP/*physiology [MESH]
  • |Humans [MESH]
  • |International Agencies [MESH]
  • |Ligands [MESH]
  • |Pharmacology, Clinical/trends [MESH]
  • |Pharmacology/trends [MESH]
  • |Protein Isoforms/agonists/chemistry/classification/metabolism [MESH]
  • |Receptors, G-Protein-Coupled/agonists/chemistry/classification/*metabolism [MESH]
  • |Receptors, Peptide/agonists/chemistry/classification/*metabolism [MESH]
  • |Relaxin/agonists/analogs & derivatives/antagonists & inhibitors/*metabolism [MESH]
  • |Societies, Scientific [MESH]


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