International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

Bathgate, Ross A. D.; Ivell, Richard; Sanborn, Barbara M.; Sherwood, O. D.; Summers, Roger J.

doi:10.1124/pr.58.1.9

Cited by 291 publications

(274 citation statements)

References 224 publications

(334 reference statements)

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“…The closely related insulin-like 3 peptide receptor RXFP2 also responds to higher doses of RLN by cAMP increase in cells transfected with RXFP2 (Feng et al 2007), however, such crossreactivity was not detected in vivo (Kamat et al 2004. Despite significant variations in the amino acid sequence of different mammalian RLN peptides, they all efficiently cross-activate human RXFP1 (Sherwood 2004, Bathgate et al 2006. Recently, it was demonstrated that an analog of RLN peptide with a mutated receptor-binding domain has a moderately suppressive effect on prostate tumor when stably or transiently expressed in prostate cancer cells (Silvertown et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…New roles for RLN in various other physiological scenarios have recently been established. These include regulation of connective tissue remodeling and fibrosis, promotion of angiogenesis, blood vessels dilation, chronotropic action in the heart, wound healing, inhibition of apoptosis, and other physiological effects (Sherwood 2004, Bathgate et al 2006. There are two almost identical RLN genes in the genome of great apes and humans (RLN1 and RLN2); all other studied mammalian species have only one copy of the orthologous gene (Klonisch et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…RLN family peptide receptor 1 (RXFP1) is a G-proteincoupled receptor expressed on the cell surface (Hsu et al 2002). Stimulation of RXFP1 with RLN causes a cAMP increase mediated through G s /G i proteins and protein kinase A in some cells (Bathgate et al 2006). In addition, the involvement of tyrosine kinases, protein kinase C zeta, phosphatidylinositol 3-kinase (PI3K), and other molecules in RLN signaling was also demonstrated (Bathgate et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Stimulation of RXFP1 with RLN causes a cAMP increase mediated through G s /G i proteins and protein kinase A in some cells (Bathgate et al 2006). In addition, the involvement of tyrosine kinases, protein kinase C zeta, phosphatidylinositol 3-kinase (PI3K), and other molecules in RLN signaling was also demonstrated (Bathgate et al 2006). RLN regulates a number of critical molecules directly relevant to tumor progression.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Feng

Agoulnik

Truong

et al. 2010

Endocrine-Related Cancer

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Relaxin (RLN) is a small peptide hormone expressed in several cancers of reproductive and endocrine organs. Increased expression of RLN in prostate cancer correlates with aggressive cancer. RLN G-protein-coupled receptor (RLN family peptide receptor 1, RXFP1) is expressed in both androgen receptor (AR)-positive and -negative prostate cancers as well as in prostate cancer cell lines. RLN behaves as a cell growth factor and increases invasiveness and proliferation of cancer cells in vitro and in vivo. The objective of this study is to determine whether downregulation of RXFP1 expression using small interfering RNA (siRNA) reduces cancer growth and metastasis in a xenograft model of prostate cancer. We used two well-characterized prostate adenocarcinoma cell lines, AR-positive LNCaP cells and AR-negative PC3 cells. The tumors were established in nude male mice by s.c. injections. Intratumoral injections of siRNAs loaded on biodegradable chitosan nanoparticles led to a downregulation of RXFP1 receptor expression and a dramatic reduction in tumor growth. In LNCaP tumors, the siRNA treatment led to an extensive necrosis. In PC3 xenografts treated with siRNA against RXFP1, the smaller tumor size was associated with the decreased cell proliferation and increased apoptosis. The downregulation of RXFP1 resulted in significant decrease in metastasis rate in PC3 tumors. Global transcriptional profiling of PC3 cells treated with RXFP1 siRNA revealed genes with significantly altered expression profiles previously shown to promote tumorigenesis, including the downregulation of MCAM, MUC1, ANGPTL4, GPI, and TSPAN8. Thus, the suppression of RLN/RXFP1 may have potential therapeutic benefits in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Feng

Agoulnik

Truong

et al. 2010

Endocrine-Related Cancer

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“…Relaxin-3 is the highly conserved, ancestral neuropeptide of the relaxin/insulin superfamily, and its cognate G-protein-coupled receptor is relaxin family peptide 3 receptor (RXFP3) (11)(12)(13)(14)(15)(16). Relaxin-3 is predominantly expressed in gamma-aminobutyric acid (GABA) neurons in the hindbrain nucleus incertus, which projects widely to forebrain areas, including the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus, and lateral hypothalamus, which also express high levels of RXFP3 (11,15,(17)(18)(19)(20)(21)(22).…”

Section: Addiction | Dependencementioning

confidence: 99%

Relaxin-3/RXFP3 system regulates alcohol-seeking

Ryan

Kastman

Krstew

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

114

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Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. Using a rat model of alcohol use and alcohol-seeking, we demonstrated that central administration of peptide antagonists for relaxin family peptide 3 receptor (RXFP3), the cognate receptor for the highly conserved neuropeptide, relaxin-3, decreased selfadministration of alcohol in a dose-related manner and attenuated cue-and stress-induced reinstatement following extinction. By comparison, RXFP3 antagonist treatment did not significantly attenuate self-administration or reinstatement of sucrose-seeking, suggesting a selective effect for alcohol. RXFP3 is densely expressed in the stress-responsive bed nucleus of the stria terminalis, and bilateral injections of RXFP3 antagonist into the bed nucleus of the stria terminalis significantly decreased self-administration and stress-induced reinstatement of alcohol, suggesting that this brain region may, at least in part, mediate the effects of RXFP3 antagonism. RXFP3 antagonist treatment had no effect on general ingestive behavior, activity, or procedural memory for lever pressing in the paradigms assessed. These data suggest that relaxin-3/ RXFP3 signaling regulates alcohol intake and relapse-like behavior, adding to current knowledge of the brain chemistry of rewardseeking. addiction | dependenceA lcohol abuse is a major cause of morbidity and mortality worldwide, accounting for an estimated 3.8% of all global deaths and 4.6% of the global burden of disease and injury (1). Excessive alcohol use may also lead to alcohol dependence (also termed "alcohol addiction") (2, 3), which has a lifetime prevalence of ∼12.5% (4). Economic costs due to alcohol abuse were in the order of $235 billion in the United States in 2007, or ∼2.7% of GDP (1, 5). Despite the huge impact of alcohol use disorders on society, current first-line therapeutic agents, such as naltrexone and acamprosate, are far from adequate, with high relapse rates during treatment and problems with compliance (6-8). New therapeutic agents are clearly required, particularly for the reduction of hazardous drinking and prevention of relapse (9). To this end, a major goal in addiction neuroscience is to understand the neurobiology and neurocircuitry affected by alcohol use disorders and to identify factors implicated in these conditions, which may lead to improved and more targeted therapies (7-10). Here we investigate the neuropeptide relaxin-3 for its involvement in rodent models of alcohol-seeking and consumption.Relaxin-3 is the highly conserved, ancestral neuropeptide of the relaxin/insulin superfamily, and its cognate G-protein-coupled receptor is relaxin family peptide 3 receptor (RXFP3) (11-16). Relaxin-3 is predominantly expressed in gamma-aminobutyric acid (GABA) neurons in the hindbrain nucleus incertus, which projects widely to forebrain areas, including the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus, and lateral hypothalamus, which also express high levels ...

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Endogenous Vasoactive Peptides

Webb

Ksander²

2010

Burger's Medicinal Chemistry and Drug Discovery

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The control of vasomotor tone regulates the overall cardiovascular system and its responses to physiological and pathophysiological stress. It provides differential blood flow to regional vascular beds under normal physiologic conditions, at times of normal stress, such as exercise, and during conditions of pathological stress, such as congestive heart failure. Although the vascular system regulates many of its functions at the site of the blood vessel itself, other factors that may control vascular tone include the autonomic nervous system, circulating hormones functioning in an endocrine role, and reflex metabolic control. Many newly discovered peptides were found to be widespread in autonomic and sensory neurons innervating the vasculature, and they possess potent vasoactive effects on many blood vessels. Vasoactive peptides have been shown to play an important role in many pathological situations, for example, asthma, arthritis, vascular headaches, hypertension, and other cardiovascular diseases. In this chapter, we will outline the evidence for the different actions of various vasoactive peptides, their interaction with other systems, the possible role they have in diseases, and the present and future therapeutic use of vasoactive peptide agonists and antagonists.

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International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

Cited by 291 publications

References 224 publications

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Relaxin-3/RXFP3 system regulates alcohol-seeking

Endogenous Vasoactive Peptides

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