Human relaxin-2 ("relaxin"), originally identified as a peptidic hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic and angiogenic effects in both males and females. It belongs to the so-called relaxin peptide family which includes the insulin-like peptides INSL3 and INSL5, and relaxin-3 (H3) as well as relaxin. INSL3 has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. These members of relaxin peptide family exert such effects binding to different kinds of receptors, classified as relaxin family peptide (RXFP) receptors: RXFP1, RXFP2, RXFP3, and RXFP4. These G protein-coupled receptors predominantly bind relaxin, INSL3, relaxin-3, and INSL-5, respectively. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Both RXFP3 and RXFP4 inhibit cAMP production, and RXFP3 activate MAP kinases.

Organismal Systems; Endocrine system

Homo sapiens (human) [GN:hsa]

PMID:23303914

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Physiol Rev 93:405-80 (2013)
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PMID:23401142

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Med Res Rev 34:77-105 (2014)
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PMID:18675759

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Drug Discov Today 13:640-51 (2008)
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PMID:17293890

Halls ML, van der Westhuizen ET, Bathgate RA, Summers RJ

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Br J Pharmacol 150:677-91 (2007)
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PMID:16507880

Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ

International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides.

Pharmacol Rev 58:7-31 (2006)
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PMID:19935741

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Cardiovascular effects of relaxin: from basic science to clinical therapy.

Nat Rev Cardiol 7:48-58 (2010)
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PMID:12646076

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Reprod Biol Endocrinol 1:5 (2003)

PMID:17458501

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Cell Mol Life Sci 64:1539-57 (2007)
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PMID:23883673

Sasser JM

The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease.

Am J Physiol Regul Integr Comp Physiol 305:R559-65 (2013)
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PMID:27239943

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Br J Pharmacol 174:933-949 (2017)
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PMID:15956688

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Receptors for relaxin family peptides.

Ann N Y Acad Sci 1041:61-76 (2005)
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PMID:22936987

Chow BS, Chew EG, Zhao C, Bathgate RA, Hewitson TD, Samuel CS

Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS.

PLoS One 7:e42714 (2012)
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PMID:16814863

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Pharmacol Ther 112:529-52 (2006)
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PMID:25759289

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Relaxin: a novel agent for the treatment of acute heart failure.

Pharmacotherapy 35:315-27 (2015)
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PMID:16569707

Halls ML, Bathgate RA, Summers RJ

Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms.

Mol Pharmacol 70:214-26 (2006)
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PMID:26294284

Kocan M, Ang SY, Summers RJ

Orthosteric, Allosteric and Biased Signalling at the Relaxin-3 Receptor RXFP3.

Neurochem Res 41:610-9 (2016)
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PMID:17351017

van der Westhuizen ET, Werry TD, Sexton PM, Summers RJ

The relaxin family peptide receptor 3 activates extracellular signal-regulated kinase 1/2 through a protein kinase C-dependent mechanism.

Mol Pharmacol 71:1618-29 (2007)
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