Log in

Relevant bibliographies by topics / Relaxin family peptpide receptors / Journal articles

Journal articles on the topic 'Relaxin family peptpide receptors'

To see the other types of publications on this topic, follow the link: Relaxin family peptpide receptors.

Author: Grafiati

Published: 10 December 2022

Last updated: 29 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 49 journal articles for your research on the topic 'Relaxin family peptpide receptors.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Bathgate, R. A. D., M. L. Halls, E. T. van der Westhuizen, G. E. Callander, M. Kocan, and R. J. Summers. "Relaxin Family Peptides and Their Receptors." Physiological Reviews 93, no. 1 (January 2013): 405–80. http://dx.doi.org/10.1152/physrev.00001.2012.

Full text

Abstract:

There are seven relaxin family peptides that are all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Insulin-like peptide-3 (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. Although they are structurally related to insulin, the relaxin family peptides produce their physiological effects by activating a group of four G protein-coupled receptors (GPCRs), relaxin family peptide receptors 1–4 (RXFP1–4). Relaxin and INSL3 are the cognate ligands for RXFP1 and RXFP2, respectively, that are leucine-rich repeat containing GPCRs. 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. Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and activate MAP kinases. Although there are still many unanswered questions regarding the mode of action of relaxin family peptides, it is clear that they have important physiological roles that could be exploited for therapeutic benefit.

APA, Harvard, Vancouver, ISO, and other styles

2

BATHGATE, ROSS A., RICHARD IVELL, BARBARA M. SANBORN, O. DAVID SHERWOOD, and ROGER J. SUMMERS. "Receptors for Relaxin Family Peptides." Annals of the New York Academy of Sciences 1041, no. 1 (May 2005): 61–76. http://dx.doi.org/10.1196/annals.1282.010.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Gundlach, Andrew L., Sherie Ma, Qian Sang, Pei-Juan Shen, Loretta Piccenna, Katayoun Sedaghat, Craig M. Smith, et al. "Relaxin Family Peptides and Receptors in Mammalian Brain." Annals of the New York Academy of Sciences 1160, no. 1 (April 2009): 226–35. http://dx.doi.org/10.1111/j.1749-6632.2009.03956.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Kong, Roy C. K., Patrick J. Shilling, Derek K. Lobb, Paul R. Gooley, and Ross A. D. Bathgate. "Membrane receptors: Structure and function of the relaxin family peptide receptors." Molecular and Cellular Endocrinology 320, no. 1-2 (May 2010): 1–15. http://dx.doi.org/10.1016/j.mce.2010.02.003.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

van der Westhuizen, Emma T., Michelle L. Halls, Chrishan S. Samuel, Ross A. D. Bathgate, Elaine N. Unemori, Steven W. Sutton, and Roger J. Summers. "Relaxin family peptide receptors – from orphans to therapeutic targets." Drug Discovery Today 13, no. 15-16 (August 2008): 640–51. http://dx.doi.org/10.1016/j.drudis.2008.04.002.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Svendsen, Angela Manegold, Milka Vrecl, Louise Knudsen, Anders Heding, John D. Wade, Ross A. D. Bathgate, Pierre De Meyts, and Jane Nøhr. "Dimerization and Negative Cooperativity in the Relaxin Family Peptide Receptors." Annals of the New York Academy of Sciences 1160, no. 1 (April 2009): 54–59. http://dx.doi.org/10.1111/j.1749-6632.2009.03835.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Scott, Daniel J., Tracey Wilkinson, Geoffrey W. Tregear, and Ross A. D. Bathgate. "The relaxin peptide family and their novel G-protein coupled receptors." International Journal of Peptide Research and Therapeutics 10, no. 5-6 (November 2003): 393–400. http://dx.doi.org/10.1007/s10989-004-2389-4.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Scott, Daniel J., Tracey Wilkinson, Geoffrey W. Tregear, and Ross A. D. Bathgate. "The relaxin peptide family and their novel G-protein coupled receptors." Letters in Peptide Science 10, no. 5-6 (September 2003): 393–400. http://dx.doi.org/10.1007/bf02442569.

Full text

APA, Harvard, Vancouver, ISO, and other styles

9

Kania, Alan, Marian H. Lewandowski, and Anna Błasiak. "Relaxin-3 and relaxin family peptide receptors – from structure to functions of a newly discovered mammalian brain system." Postępy Higieny i Medycyny Doświadczalnej 68 (June 24, 2014): 851–64. http://dx.doi.org/10.5604/17322693.1110163.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Chen, Catherine Z., Noel Southall, Jingbo Xiao, Juan J. Marugan, Marc Ferrer, Xin Hu, Raisa E. Jones, et al. "Identification of Small-Molecule Agonists of Human Relaxin Family Receptor 1 (RXFP1) by Using a Homogenous Cell-Based cAMP Assay." Journal of Biomolecular Screening 18, no. 6 (December 4, 2012): 670–77. http://dx.doi.org/10.1177/1087057112469406.

Full text

Abstract:

The relaxin hormone is involved in a variety of biological functions, including female reproduction and parturition, as well as regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein–coupled receptor (GPCR) relaxin family receptor 1 (RXFP1) is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. Although agonists of the receptor could have a wide range of pharmacologic utility, until now there have been no reported small-molecule agonists for relaxin receptors. Here, we report the development of a quantitative high-throughput platform for an RXFP1 agonist screen based on homogenous cell-based HTRF cyclic AMP (cAMP) assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365 677 compounds. Neither compound showed activity in a counterscreen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small-molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists.

APA, Harvard, Vancouver, ISO, and other styles

11

Callander, Gabrielle E., Walter G. Thomas, and Ross A. D. Bathgate. "Prolonged RXFP1 and RXFP2 signaling can be explained by poor internalization and a lack of β-arrestin recruitment." American Journal of Physiology-Cell Physiology 296, no. 5 (May 2009): C1058—C1066. http://dx.doi.org/10.1152/ajpcell.00581.2008.

Full text

Abstract:

Relaxin induces sustained physiological responses, which brings into question the deactivation processes typical of most G protein-coupled receptors (GPCR) for its receptor, relaxin family peptide receptor 1 (RXFP1). Here, we examined relaxin-dependent phosphorylation of RXFP1 and the related insulin-like peptide 3 (INSL3) receptor, RXFP2, as well as the capacity of these receptors to recruit β-arrestins and internalize in response to ligand stimulation. We confirmed in human embryonic kidney (HEK)-293T cells, expressing RXFP1 or RXFP2, that both receptors elicit prolonged cAMP responses up to 6 h after stimulation. Receptors immunoprecipitated from 32P metabolically labeled cells were used to investigate the agonist-specific phosphorylation. Rapid and robust receptor phosphorylation was not observed for either RXFP1 or RXFP2, although some 32P-incorporation was observed at 30 min; however, this was not statistically significant. In accord with this result, RXFP1 and RXFP2 demonstrated poor internalization in response to relaxin or INSL3, as compared with the angiotensin II type 1 receptor (AT1R), which undergoes rapid and robust phosphorylation and internalization in response to angiotensin II. Additionally, coexpression of GPCR kinases has no effect on the rate of internalization for either RXFP1 or RXFP2. Confocal microscopy was used to follow the trafficking of green fluorescent protein-labeled β-arrestins after receptor activation. Neither RXFP1 nor RXFP2 activation results in recruitment of β-arrestins to the cell surface, whereas AT1R rapidly recruits both β-arrestins-1 and -2. The apparent lack of classical regulation for RXFP1 and RXFP2 provides the molecular basis for the prolonged signaling and physiological actions of relaxin and related peptides.

APA, Harvard, Vancouver, ISO, and other styles

12

Summers, R. J. "Recent progress in the understanding of relaxin family peptides and their receptors." British Journal of Pharmacology 174, no. 10 (April 26, 2017): 915–20. http://dx.doi.org/10.1111/bph.13778.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Vodstrcil, Lenka A., Mary E. Wlodek, and Laura J. Parry. "Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and Lgr8, in the uterus of late pregnant rats." Reproduction, Fertility and Development 19, no. 4 (2007): 530. http://dx.doi.org/10.1071/rd07007.

Full text

Abstract:

The peptide hormone relaxin stimulates uterine growth and endometrial angiogenesis and inhibits myometrial contractions in a variety of species. The receptor for relaxin is a leucine-rich repeat containing G-protein-coupled receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant mice, with a significant decrease in receptor density observed at term. The present study first compared the expression of Lgr7 with another relaxin-family receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats. The uterus was separated into endometrial and myometrial components, and the myometrium into fetal and non-fetal sites, for further analysis. We then assessed the response of these receptors to uteroplacental restriction (UPR). Expression of the Lgr7 gene was significantly higher in the uterus compared with the placenta. Within the uterus, on Day 20 of gestation, there was equivalent expression of Lgr7 in fetal and non-fetal sites of the myometrium, as well as in the endometrium v. myometrium. The second receptor investigated, Lgr8, was also expressed in the endometrium and myometrium, but at significantly lower levels than Lgr7. Bilateral ligation of the maternal uterine blood vessels on Day 18 of gestation resulted in uteroplacental restriction, a decrease in fetal weight and litter size, and a significant upregulation in uterine, but not placental, Lgr7 and Lgr8 gene expression in UPR animals compared with controls. These data suggest that both relaxin family receptors are upregulated in response to a reduction in uteroplacental blood flow in rats.

APA, Harvard, Vancouver, ISO, and other styles

14

Hossain, Mohammed Akhter, K. Johan Rosengren, Linda M. Haugaard-Jönsson, Soude Zhang, Sharon Layfield, Tania Ferraro, Norelle L. Daly, Geoffrey W. Tregear, John D. Wade, and Ross A. D. Bathgate. "The A-chain of Human Relaxin Family Peptides Has Distinct Roles in the Binding and Activation of the Different Relaxin Family Peptide Receptors." Journal of Biological Chemistry 283, no. 25 (April 22, 2008): 17287–97. http://dx.doi.org/10.1074/jbc.m801911200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Halls, Michelle L., Courtney P. Bond, Satoko Sudo, Jin Kumagai, Tania Ferraro, Sharon Layfield, Ross A. D. Bathgate, and Roger J. Summers. "Multiple Binding Sites Revealed by Interaction of Relaxin Family Peptides with Native and Chimeric Relaxin Family Peptide Receptors 1 and 2 (LGR7 and LGR8)." Journal of Pharmacology and Experimental Therapeutics 313, no. 2 (January 12, 2005): 677–87. http://dx.doi.org/10.1124/jpet.104.080655.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Scott, Daniel J., K. Johan Rosengren, and Ross A. D. Bathgate. "The Different Ligand-Binding Modes of Relaxin Family Peptide Receptors RXFP1 and RXFP2." Molecular Endocrinology 26, no. 11 (November 1, 2012): 1896–906. http://dx.doi.org/10.1210/me.2012-1188.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Halls, Michelle L., Ross A. D. Bathgate, and Roger J. Summers. "Relaxin Family Peptide Receptors RXFP1 and RXFP2 Modulate cAMP Signaling by Distinct Mechanisms." Molecular Pharmacology 70, no. 1 (March 28, 2006): 214–26. http://dx.doi.org/10.1124/mol.105.021691.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

McGowan, B. M., S. A. Stanley, N. E. White, A. Spangeus, M. Patterson, E. L. Thompson, K. L. Smith, et al. "Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats." American Journal of Physiology-Endocrinology and Metabolism 292, no. 3 (March 2007): E913—E919. http://dx.doi.org/10.1152/ajpendo.00346.2006.

Full text

Abstract:

The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4 ± 0.2 (vehicle) vs. 2.9 ± 0.5 g (H3), P < 0.001; ARC 0.7 ± 0.3 (vehicle) vs. 2.7 ± 0.2 g (H3), P < 0.05; and APOA 0.8 ± 0.1 (vehicle) vs. 2.2 ± 0.2 g (H3), P < 0.05]. Cumulative food intake was significantly increased ≤8 h following administration into the SON and 4 h into the APOA. A significant increase in Fos-like immunoreactivity was seen in the SON following central relaxin-3 administration. Relaxin-3 stimulates feeding in several hypothalamic nuclei, and these studies provide additional support for relaxin-3 as an important peptide in appetite regulation.

APA, Harvard, Vancouver, ISO, and other styles

19

Feugang, J. M., J. C. Rodriguez-Muñoz, R. Black, S. Willard, and P. Ryan. "267 EXPRESSION OF RELAXIN FAMILY PEPTIDE RECEPTORS RXFP1 AND RXFP2 IN PIG PREIMPLANTATION EMBRYOS AND DEVELOPMENTAL EFFECTS OF RELAXIN HORMONE." Reproduction, Fertility and Development 22, no. 1 (2010): 290. http://dx.doi.org/10.1071/rdv22n1ab267.

Full text

Abstract:

Relaxin is a polypeptide hormone secreted by male and female reproductive tissues to facilitate spermatozoa progression in the female tract and parturition. Relaxin secretions are found in the vicinity of oocytes and embryos, and exert their effects through membrane receptors, which have not yet been described in porcine embryos. Here, we determined the presence of RXFP1 and RXFP2 receptors in porcine gametes and embryo, and evaluated the developmental effects of porcine relaxin (pRLX; Yan et al. 2006 Reproduction 131, 943-950). Cumulus-oocyte complexes (COC) were aspirated from sows ovaries collected at a local abattoir. Homogeneous COC were selected for IVM (44 h) and fertilization (6 to 8 h). Presumptive zygotes were cultured in NCSU-23 + 0.4% BSA for up to 7 days. All procedures were done at 39°C, under 5% CO2 in a humidified atmosphere. Matured oocytes, BTS-diluted spermatozoa, and embryos were collected for gene expression studies. For developmental studies, COC were matured (experiment 1), or embryos cultured from the zygote stage (experiment 2) in the presence ofpRLX (0, 20, or 40 ng mL-1). In experiment 3, zygotes derived from oocytes matured in the presence of pRLX (40 ng mL-1) were cultured with pRLX (20 or 40 ng mL-1). The pRLX effects were assessed on cleaved embryos and blastocysts recorded on Days 2 and 7 postinsemination, respectively. The total cell numbers of Day-7 blastocysts were also evaluated. All data were analyzed using ANOVA. Gametes and embryos expressed RXFP1 and RXFP2 at both the mRNA and protein level. The amounts of both gene transcripts were higher in mature oocytes (metaphase II) compared with spermatozoa (P < 0.05). The RXFP1/2 mRNA ratios were in favor of RXFP2 in mature oocytes (0.9×), zygotes (0.8 ×), and cleaved embryos (0.8×), and for RXFP1 in spermatozoa (1.1 ×) and blastocysts (1.1 ×). A similar pattern during embryo development was revealed at the protein level, showing a higher RXFP2 fluorescence signal in cleaved embryos and a lower signal in blastocysts compared with RXFP1 protein. In experiment 1, COC exposed to 40 ng mL-1 pRLX resulted in fewer cleaved embryos (36 ± 4%) compared with controls (42 ± 5%, P < 0.05). Of the 40 ng mL-1 pRLX-derived cleaved embryos, a greater proportion developed to the blastocyst stage (38 ± 6%; P < 0.05) compared with control and 20 ng mL-1 pRLX-derived cleaved embryos (26 ± 4% and 17 ± 8%, respectively). In experiment 2, however, 40 ng mL-1 pRLX induced higher cleavage but lower blastocyst rates (51 ± 5% and 20 ± 4%, respectively) compared with the control group (37 ± 4% and 32 ± 7%, respectively) (P < 0.05). In experiment 3, the exposure of both oocytes and derived embryos did not affect the developmental rates (P > 0.05). Nevertheless, pRLX significantly increased the mean cell number of blastocysts in all experiments (P < 0.05). We concluded that pig embryos express RXFP1 and RXFP2 receptors, which may facilitate a role for pRLX during oocyte maturation and embryo development in the pig. This work was supported by the USDA-ARS Biophotonics Initiative project# 58-6402-3-0120 and the Mississippi Agricultural and Forestry Experiment Station (MAFES).

APA, Harvard, Vancouver, ISO, and other styles

20

Bergeron, Lindsay H., Jordan M. Willcox, Faisal J. Alibhai, Barry J. Connell, Tarek M. Saleh, Brian C. Wilson, and Alastair J. S. Summerlee. "Relaxin Peptide Hormones Are Protective During the Early Stages of Ischemic Stroke in Male Rats." Endocrinology 156, no. 2 (December 2, 2014): 638–46. http://dx.doi.org/10.1210/en.2014-1676.

Full text

Abstract:

The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke.

APA, Harvard, Vancouver, ISO, and other styles

21

ORTINAU, STEFANIE, FENG LIN, JOHN D. WADE, GEOFFREY W. TREGEAR, ROSS A. D. BATHGATE, and ANDREW L. GUNDLACH. "Insulin-Relaxin Family Peptide Signaling and Receptors in Mouse Brain Membranes and Neuronal Cells." Annals of the New York Academy of Sciences 1041, no. 1 (May 2005): 211–15. http://dx.doi.org/10.1196/annals.1282.032.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Halls, Michelle L., Ross A. D. Bathgate, Steve W. Sutton, Thomas B. Dschietzig, and Roger J. Summers. "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." Pharmacological Reviews 67, no. 2 (March 11, 2015): 389–440. http://dx.doi.org/10.1124/pr.114.009472.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Kern, András, Alexander I. Agoulnik, and Gillian D. Bryant-Greenwood. "The Low-Density Lipoprotein Class A Module of the Relaxin Receptor (Leucine-Rich Repeat Containing G-Protein Coupled Receptor 7): Its Role in Signaling and Trafficking to the Cell Membrane." Endocrinology 148, no. 3 (March 1, 2007): 1181–94. http://dx.doi.org/10.1210/en.2006-1086.

Full text

Abstract:

The relaxin receptor (LGR7, relaxin family peptide receptor 1) is a member of the leucine-rich repeat containing G protein-coupled receptors subgroup C. This and the LGR8 (relaxin family peptide receptor 2) receptor are unique in having a low-density lipoprotein class A (LDL-A) module at their N termini. This study was designed to show the role of the LDL-A in LGR7 expression and function. Point mutants for the conserved cysteines (Cys47 and Cys53) and for calcium binding asparagine (Asp58), a mutant with deleted LDL-A domain and chimeric LGR7 receptor with LGR8 LDL-A all showed no cAMP response to human relaxins H1 or H2. We have shown that their cell surface delivery was uncompromised. The mutation of the putative N-linked glycosylation site (Asn36) decreased cAMP production and reduced cell surface expression to 37% of the wild-type LGR7. All point mutant, chimeric, and wild-type receptor proteins were expressed as the two forms. The immature or precursor form of the receptor was 80 kDa, whereas the mature receptor, delivered to the cell surface was 95 kDa. The glycosylation mutant was also expressed as two forms with appropriately smaller molecular masses. Deletion of the LDL-A module resulted in expression of the mature receptor only. These data suggest that the LDL-A module of LGR7 influences receptor maturation, cell surface expression, and relaxin-activated signal transduction.

APA, Harvard, Vancouver, ISO, and other styles

24

Good, Sara, Sergey Yegorov, Joran Martijn, Jens Franck, and Jan Bogerd. "New Insights into Ligand-Receptor Pairing and Coevolution of Relaxin Family Peptides and Their Receptors in Teleosts." International Journal of Evolutionary Biology 2012 (September 13, 2012): 1–14. http://dx.doi.org/10.1155/2012/310278.

Full text

Abstract:

Relaxin-like peptides (RLN/INSL) play diverse roles in reproductive and neuroendocrine processes in placental mammals and are functionally associated with two distinct types of receptors (RXFP) for each respective function. The diversification of RLN/INSL and RXFP gene families in vertebrates was predominantly driven by whole genome duplications (2R and 3R). Teleosts preferentially retained duplicates of genes putatively involved in neuroendocrine regulation, harboring a total of 10-11 receptors and 6 ligand genes, while most mammals have equal numbers of ligands and receptors. To date, the ligand-receptor relationships of teleost Rln/Insl peptides and their receptors have largely remained unexplored. Here, we use selection analyses based on sequence data from 5 teleosts and qPCR expression data from zebrafish to explore possible ligand-receptor pairings in teleosts. We find support for the hypothesis that, with the exception of RLN, which has undergone strong positive selection in mammalian lineages, the ligand and receptor genes shared between mammals and teleosts appear to have similar pairings. On the other hand, the teleost-specific receptors show evidence of subfunctionalization. Overall, this study underscores the complexity of RLN/INSL and RXFP ligand-receptor interactions in teleosts and establishes theoretical background for further experimental work in nonmammals.

APA, Harvard, Vancouver, ISO, and other styles

25

Bathgate, Ross A., Richard Ivell, Barbara M. Sanborn, O. David Sherwood, and Roger J. Summers. "International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides." Pharmacological Reviews 58, no. 1 (February 28, 2006): 7–31. http://dx.doi.org/10.1124/pr.58.1.9.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Lee, Jasinda H., Shu Qing Koh, Simone Guadagna, Paul T. Francis, Margaret M. Esiri, Christopher P. Chen, Peter T. H. Wong, Gavin S. Dawe, and Mitchell K. P. Lai. "Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer’s disease patients." Psychopharmacology 233, no. 4 (November 6, 2015): 591–98. http://dx.doi.org/10.1007/s00213-015-4131-7.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Halls, M. L., E. T. van der Westhuizen, R. A. D. Bathgate, and R. J. Summers. "Relaxin Family Peptide Receptors - former orphans reunite with their parent ligands to activate multiple signalling pathways." British Journal of Pharmacology 150, no. 6 (March 2007): 677–91. http://dx.doi.org/10.1038/sj.bjp.0707140.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Valkovic, Adam L., Miranda B. Leckey, Alice R. Whitehead, Mohammed A. Hossain, Asuka Inoue, Martina Kocan, and Ross A. D. Bathgate. "Real-time examination of cAMP activity at relaxin family peptide receptors using a BRET-based biosensor." Pharmacology Research & Perspectives 6, no. 5 (September 24, 2018): e00432. http://dx.doi.org/10.1002/prp2.432.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Halls, Michelle L., Ross A. D. Bathgate, and Roger J. Summers. "Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes." Journal of Pharmacology and Experimental Therapeutics 320, no. 1 (October 25, 2006): 281–90. http://dx.doi.org/10.1124/jpet.106.113225.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Good, Sara, Sergey Yegorov, Joran Martijn, Jens Franck, and Jan Bogerd. "Erratum to “New Insights into Ligand-Receptor Pairing and Coevolution of Relaxin Family Peptides and Their Receptors in Teleosts”." International Journal of Evolutionary Biology 2013 (April 24, 2013): 1–3. http://dx.doi.org/10.1155/2013/807326.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Chow, Bryna S. M., Martina Kocan, Matthew Shen, Yan Wang, Lei Han, Jacqueline Y. Chew, Chao Wang, et al. "AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis." Journal of the American Society of Nephrology 30, no. 11 (September 11, 2019): 2191–207. http://dx.doi.org/10.1681/asn.2019060597.

Full text

Abstract:

BackgroundRecombinant human relaxin-2 (serelaxin), which has organ-protective actions mediated via its cognate G protein–coupled receptor relaxin family peptide receptor 1 (RXFP1), has emerged as a potential agent to treat fibrosis. Studies have shown that serelaxin requires the angiotensin II (AngII) type 2 receptor (AT2R) to ameliorate renal fibrogenesis in vitro and in vivo. Whether its antifibrotic actions are affected by modulation of the AngII type 1 receptor (AT1R), which is expressed on myofibroblasts along with RXFP1 and AT2R, is unknown.MethodsWe examined the signal transduction mechanisms of serelaxin when applied to primary rat renal and human cardiac myofibroblasts in vitro, and in three models of renal- or cardiomyopathy-induced fibrosis in vivo.ResultsThe AT1R blockers irbesartan and candesartan abrogated antifibrotic signal transduction of serelaxin via RXFP1 in vitro and in vivo. Candesartan also ameliorated serelaxin’s antifibrotic actions in the left ventricle of mice with cardiomyopathy, indicating that candesartan’s inhibitory effects were not confined to the kidney. We also demonstrated in a transfected cell system that serelaxin did not directly bind to AT1Rs but that constitutive AT1R–RXFP1 interactions could form. To potentially explain these findings, we also demonstrated that renal and cardiac myofibroblasts expressed all three receptors and that antagonists acting at each receptor directly or allosterically blocked the antifibrotic effects of either serelaxin or an AT2R agonist (compound 21).ConclusionsThese findings have significant implications for the concomitant use of RXFP1 or AT2R agonists with AT1R blockers, and suggest that functional interactions between the three receptors on myofibroblasts may represent new targets for controlling fibrosis progression.

APA, Harvard, Vancouver, ISO, and other styles

32

Tapia Cáceres, Felipe, Tracey A. Gaspari, Mohammed Akhter Hossain, and Chrishan S. Samuel. "Relaxin Inhibits the Cardiac Myofibroblast NLRP3 Inflammasome as Part of Its Anti-Fibrotic Actions via the Angiotensin Type 2 and ATP (P2X7) Receptors." International Journal of Molecular Sciences 23, no. 13 (June 25, 2022): 7074. http://dx.doi.org/10.3390/ijms23137074.

Full text

Abstract:

Chronic NLRP3 inflammasome activation can promote fibrosis through its production of interleukin (IL)-1β and IL-18. Conversely, recombinant human relaxin (RLX) can inhibit the pro-fibrotic interactions between IL-1β, IL-18 and transforming growth factor (TGF)-β1. Here, the broader extent by which RLX targeted the myofibroblast NLRP3 inflammasome to mediate its anti-fibrotic effects was elucidated. Primary human cardiac fibroblasts (HCFs), stimulated with TGF-β1 (to promote myofibroblast (HCMF) differentiation), LPS (to prime the NLRP3 inflammasome) and ATP (to activate the NLRP3 inflammasome) (T+L+A) or benzoylbenzoyl-ATP (to activate the ATP receptor; P2X7R) (T+L+Bz), co-expressed relaxin family peptide receptor-1 (RXFP1), the angiotensin II type 2 receptor (AT2R) and P2X7R, and underwent increased protein expression of toll-like receptor (TLR)-4, NLRP3, caspase-1, IL-1β and IL-18. Whilst RLX co-administration to HCMFs significantly prevented the T+L+A- or T+L+Bz-stimulated increase in these end points, the inhibitory effects of RLX were annulled by the pharmacological antagonism of either RXFP1, AT2R, P2X7R, TLR-4, reactive oxygen species (ROS) or caspase-1. The RLX-induced amelioration of left ventricular inflammation, cardiomyocyte hypertrophy and fibrosis in isoproterenol (ISO)-injured mice, was also attenuated by P2X7R antagonism. Thus, the ability of RLX to ameliorate the myofibroblast NLRP3 inflammasome as part of its anti-fibrotic effects, appeared to involve RXFP1, AT2R, P2X7R and the inhibition of TLR-4, ROS and caspase-1.

APA, Harvard, Vancouver, ISO, and other styles

33

Yegorov, Sergey, Jan Bogerd, and Sara V. Good. "The relaxin family peptide receptors and their ligands: New developments and paradigms in the evolution from jawless fish to mammals." General and Comparative Endocrinology 209 (December 2014): 93–105. http://dx.doi.org/10.1016/j.ygcen.2014.07.014.

Full text

APA, Harvard, Vancouver, ISO, and other styles

34

Braun, B. C., K. Müller, and K. Jewgenow. "Expression profiles of relaxin family peptides and their receptors indicate their influence on spermatogenesis in the domestic cat (Felis catus)." Domestic Animal Endocrinology 52 (July 2015): 25–34. http://dx.doi.org/10.1016/j.domaniend.2015.01.005.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Mita, Masatoshi, Shin Matsubara, Tomohiro Osugi, Akira Shiraishi, Azumi Wada, and Honoo Satake. "A novel G protein-coupled receptor for starfish gonadotropic hormone, relaxin-like gonad-stimulating peptide." PLOS ONE 15, no. 11 (November 23, 2020): e0242877. http://dx.doi.org/10.1371/journal.pone.0242877.

Full text

Abstract:

Gonadotropic hormones play important regulatory roles in reproduction. Relaxin-like gonad-stimulating peptide (RGP) is a gonadotropin-like hormone in starfish. However, a receptor for RGP remains to be identified. Here, we describe the identification of an authentic receptor for RGP (RGPR) in the starfish, Patiria pectinifera. A binding assay using radioiodinated P. pectinifera RGP (PpeRGP) revealed that RGPR was expressed in ovarian follicle cells. A RGPR candidate was identified by homology-searching of transcriptome data of P. pectinifera follicle cells. Based on the contig sequences, a putative 947-amino acid PpeRGPR was cloned from follicle cells. Like the vertebrate relaxin family peptide receptors (RXFP 1 and 2), PpeRGPR was a G protein-coupled receptor that harbored a low-density lipoprotein-receptor class A motif and leucine-rich repeat sequences in the extracellular domain of the N-terminal region. Sf9 cells transfected with Gαq16-fused PpeRGPR activated calcium ion mobilization in response to PpeRGP, but not to RGP of another starfish Asterias amurensis, in a dose-dependent fashion. These results confirmed the species-specific reactivity of RGP and the cognate receptor. Thus, the present study provides evidence that PpeRGPR is a specific receptor for PpeRGP. To the best of our knowledge, this is the first report on the identification of a receptor for echinoderm RGP.

APA, Harvard, Vancouver, ISO, and other styles

36

Yegorov, Sergey, and Sara Good. "Using Paleogenomics to Study the Evolution of Gene Families: Origin and Duplication History of the Relaxin Family Hormones and Their Receptors." PLoS ONE 7, no. 3 (March 21, 2012): e32923. http://dx.doi.org/10.1371/journal.pone.0032923.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Filonzi, Marcelo, Laís C. Cardoso, Maristela T. Pimenta, Daniel BC Queiróz, Maria CW Avellar, Catarina S. Porto, and Maria FM Lazari. "Relaxin family peptide receptors Rxfp1 and Rxfp2: mapping of the mRNA and protein distribution in the reproductive tract of the male rat." Reproductive Biology and Endocrinology 5, no. 1 (2007): 29. http://dx.doi.org/10.1186/1477-7827-5-29.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Kuznetsova, L. A., S. A. Plesneva, O. V. Chistiakova, T. S. Sharova, and M. N. Pertseva. "Regulation of the adenilate cyclase signal system by peptides of the insulin family, epidermal growth factor, and leptin and its functional disturbances in lymphocytes from patients presenting with type 2 diabetes mellitus." Problems of Endocrinology 57, no. 4 (August 15, 2011): 32–36. http://dx.doi.org/10.14341/probl201157432-36.

Full text

Abstract:

This study showed for the first time the stimulating action of peptides of the insulin family, insulin-like growth factor-1, relaxin, and epidermal growth factor (EGF) on the activity of the adenilate cyclase signal system (ACSS) in lymphocytes from the subjects of the control group. These hormonal effects were enhanced in the presence of guanylimidodiphosphate (GIDP). Moreover, leptin was for the first time shown to increase adenilate cyclase activity in lymphocytes from the control subjects and inhibition of this action by antibodies against leptin receptors. The patients presenting with type 2 diabetes mellitus (DM2) showed the enhanced baseline activity of adenilate cyclase in their lymphocytes whereas its stimulation by the above hormones, both in the presence and absence of GIDP, sharply declined. The influence of leptin on adenilate cyclase activity in patients with DM2 was apparent only at its concentrations above 10–8 M; it was inhibited by antibodies to leptin receptors. The results of this study indicate that disturbances of hormonal stimulation of adenilate cyclase activity in lymphocites of diabetic patients may be due to functional defects located at the receptor level in the case of leptin and at the level of Gs protein and its coupling to adenulate cyclase in case of peptides of the insulin family and GF. These findings confirm the concept being developed by the author according to which molecular defects in the hormone-dependent ACSS system constitute one of the main causes underlying the development of DM2.

APA, Harvard, Vancouver, ISO, and other styles

39

Conrad, Kirk P. "G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention." Human Reproduction Update 22, no. 5 (July 6, 2016): 647–64. http://dx.doi.org/10.1093/humupd/dmw021.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Summers, Roger J., Ross A. D. Bathgate, John D. Wade, Emma T. Van Der Westhuizen, and Michelle L. Halls. "Roles of the Receptor, the Ligand, and the Cell in the Signal Transduction Pathways Utilized by the Relaxin Family Peptide Receptors 1-3." Annals of the New York Academy of Sciences 1160, no. 1 (April 2009): 99–104. http://dx.doi.org/10.1111/j.1749-6632.2009.03828.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Bathgate, Ross, Thomas Dschietzig, Andrew L. Gundlach, Michelle Halls, and Roger Summers. "Relaxin family peptide receptors in GtoPdb v.2021.3." IUPHAR/BPS Guide to Pharmacology CITE 2021, no. 3 (September 2, 2021). http://dx.doi.org/10.2218/gtopdb/f60/2021.3.

Full text

Abstract:

Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [18, 81]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1, relaxin, relaxin-3 (also known as INSL7), insulin-like peptide 3 (INSL3) and INSL5. Species homologues of relaxin have distinct pharmacology and relaxin interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [184]. relaxin-3 is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [183]. INSL5 is the ligand for RXFP4 but is a weak antagonist of RXFP3. relaxin and INSL3 have multiple complex binding interactions with RXFP1 [189] and RXFP2 [91] which direct the N-terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct receptor signaling [186]. INSL5 and relaxin-3 interact with their receptors using distinct residues in their B-chains for binding, and activation, respectively [225, 104].

APA, Harvard, Vancouver, ISO, and other styles

42

Bathgate, Ross, Thomas Dschietzig, Andrew L. Gundlach, Michelle Halls, and Roger Summers. "Relaxin family peptide receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database." IUPHAR/BPS Guide to Pharmacology CITE 2019, no. 4 (September 16, 2019). http://dx.doi.org/10.2218/gtopdb/f60/2019.4.

Full text

Abstract:

Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [18, 75]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1, relaxin, relaxin-3 (also known as INSL7), insulin-like peptide 3 (INSL3) and INSL5. Species homologues of relaxin have distinct pharmacology and relaxin interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [172]. relaxin-3 is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [170]. INSL5 is the ligand for RXFP4 but is a weak antagonist of RXFP3. relaxin and INSL3 have multiple complex binding interactions with RXFP1 [176] and RXFP2 [84] which direct the N-terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct receptor signaling [173]. INSL5 and relaxin-3 interact with their receptors using distinct residues in their B-chains for binding, and activation, respectively [211, 97].

APA, Harvard, Vancouver, ISO, and other styles

43

Lv, Can, Huilu Zheng, Biying Jiang, Qin Ren, Jiannan Zhang, Xin Zhang, Juan Li, and Yajun Wang. "Characterization of relaxin 3 and its receptors in chicken: Evidence for relaxin 3 acting as a novel pituitary hormone." Frontiers in Physiology 13 (November 7, 2022). http://dx.doi.org/10.3389/fphys.2022.1010851.

Full text

Abstract:

Mammalian relaxin (RLN) family peptides binding their receptors (RXFPs) play a variety of roles in many physiological processes, such as reproduction, stress, appetite regulation, and energy balance. In birds, although two relaxin family peptides (RLN3 and INSL5) and four receptors (RXFP1, RXFP2, RXFP2-like, and RXFP3) were predicated, their sequence features, signal properties, tissue distribution, and physiological functions remain largely unknown. In this study, using chickens as the experimental model, we cloned the cDNA of the cRLN3 gene and two receptor (cRXFP1 and cRXFP3) genes. Using cell-based luciferase reporter assays, we demonstrate that cRLN3 is able to activate both cRXFP1 and cRXFP3 for downstream signaling. cRXFP1, rather than cRXFP3, is a cognate receptor for cRLN3, which is different from the mammals. Tissue distribution analyses reveal that cRLN3 is highly expressed in the pituitary with lower abundance in the hypothalamus and ovary of female chicken, together with the detection that cRLN3 co-localizes with pituitary hormone genes LHB/FSHB/GRP/CART and its expression is tightly regulated by hypothalamic factors (GnRH and CRH) and sex steroid hormone (E2). The present study supports that cRLN3 may function as a novel pituitary hormone involving female reproduction.

APA, Harvard, Vancouver, ISO, and other styles

44

Dai, Yanzhenzi, Richard Ivell, Xuan Liu, Dana Janowski, and Ravinder Anand-Ivell. "Relaxin-Family Peptide Receptors 1 and 2 Are Fully Functional in the Bovine." Frontiers in Physiology 8 (June 6, 2017). http://dx.doi.org/10.3389/fphys.2017.00359.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Speck, David, Gunnar Kleinau, Mark Meininghaus, Antje Erbe, Alexandra Einfeldt, Michal Szczepek, Patrick Scheerer, and Vera Pütter. "Expression and Characterization of Relaxin Family Peptide Receptor 1 Variants." Frontiers in Pharmacology 12 (January 28, 2022). http://dx.doi.org/10.3389/fphar.2021.826112.

Full text

Abstract:

G-protein coupled receptors (GPCR) transduce extracellular stimuli into the cell interior and are thus centrally involved in almost all physiological-neuronal processes. This essential function and association with many diseases or pathological conditions explain why GPCRs are one of the priority targets in medical and pharmacological research, including structure determination. Despite enormous experimental efforts over the last decade, both the expression and purification of these membrane proteins remain elusive. This is attributable to specificities of each GPCR subtype and the finding of necessary experimental in vitro conditions, such as expression in heterologous cell systems or with accessory proteins. One of these specific GPCRs is the leucine-rich repeat domain (LRRD) containing GPCR 7 (LGR7), also termed relaxin family peptide receptor 1 (RXFP1). This receptor is characterized by a large extracellular region of around 400 amino acids constituted by several domains, a rare feature among rhodopsin-like (class A) GPCRs. In the present study, we describe the expression and purification of RXFP1, including the design of various constructs suitable for functional/biophysical studies and structure determination. Based on available sequence information, homology models, and modern biochemical and genetic tools, several receptor variations with different purification tags and fusion proteins were prepared and expressed in Sf9 cells (small-scale), followed by an analytic fluorescence-detection size-exclusion chromatography (F-SEC) to evaluate the constructs. The most promising candidates were expressed and purified on a large-scale, accompanied by ligand binding studies using surface plasmon resonance spectroscopy (SPR) and by determination of signaling capacities. The results may support extended studies on RXFP1 receptor constructs serving as targets for small molecule ligand screening or structural elucidation by protein X-ray crystallography or cryo-electron microscopy.

APA, Harvard, Vancouver, ISO, and other styles

46

Esteban-Lopez, Maria, Kenneth J. Wilson, Courtney Myhr, Elena M. Kaftanovskaya, Mark J. Henderson, Noel T. Southall, Xin Xu, et al. "Discovery of small molecule agonists of the Relaxin Family Peptide Receptor 2." Communications Biology 5, no. 1 (November 4, 2022). http://dx.doi.org/10.1038/s42003-022-04143-9.

Full text

Abstract:

AbstractThe relaxin/insulin-like family peptide receptor 2 (RXFP2) belongs to the family of class A G-protein coupled receptors (GPCRs) and it is the only known target for the insulin-like factor 3 peptide (INSL3). The importance of this ligand-receptor pair in the development of the gubernacular ligament during the transabdominal phase of testicular descent is well established. More recently, RXFP2 has been implicated in maintaining healthy bone formation. In this report, we describe the discovery of a small molecule series of RXFP2 agonists. These compounds are highly potent, efficacious, and selective RXFP2 allosteric agonists that induce gubernacular invagination in mouse embryos, increase mineralization activity in human osteoblasts in vitro, and improve bone trabecular parameters in adult mice. The described RXFP2 agonists are orally bioavailable and display favorable pharmacokinetic properties, which allow for future evaluation of the therapeutic benefits of modulating RXFP2 activation in disease models.

APA, Harvard, Vancouver, ISO, and other styles

47

Koo, Ada, Ruslan V. Pustovit, Orla R. M. Woodward, Jo E. Lewis, Fiona M. Gribble, Mohammed Akhter Hossain, Frank Reimann, and John B. Furness. "Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine." Cell and Tissue Research, May 21, 2022. http://dx.doi.org/10.1007/s00441-022-03635-8.

Full text

Abstract:

AbstractThe gastrointestinal hormone, insulin-like peptide 5 (INSL5), is found in large intestinal enteroendocrine cells (EEC). One of its functions is to stimulate nerve circuits that increase propulsive activity of the colon through its receptor, the relaxin family peptide 4 receptor (RXFP4). To investigate the mechanisms that link INSL5 to stimulation of propulsion, we have determined the localisation of cells expressing Rxfp4 in the mouse colon, using a reporter mouse to locate cells expressing the gene. The fluorescent signal indicating the location of Rxfp4 expression was in EEC, the greatest overlap of Rxfp4-dependent labelling being with cells containing 5-HT. In fact, > 90% of 5-HT cells were positive for Rxfp4 labelling. A small proportion of cells with Rxfp4-dependent labelling was 5-HT-negative, 11–15% in the distal colon and rectum, and 35% in the proximal colon. Of these, some were identified as L-cells by immunoreactivity for oxyntomodulin. Rxfp4-dependent fluorescence was also found in a sparse population of nerve endings, where it was colocalised with CGRP. We used the RXFP4 agonist, INSL5-A13, to activate the receptor and probe the role of the 5-HT cells in which it is expressed. INSL5-A13 administered by i.p. injection to conscious mice caused an increase in colorectal propulsion that was antagonised by the 5-HT3 receptor blocker, alosetron, also given i.p. We conclude that stimuli that excite INSL5-containing colonic L-cells release INSL5 that, through RXFP4, excites 5-HT release from neighbouring endocrine cells, which in turn acts on 5-HT3 receptors of enteric sensory neurons to elicit propulsive reflexes.

APA, Harvard, Vancouver, ISO, and other styles

48

de Ávila, Camila, Sandrine Chometton, Juliane Calvez, Geneviève Guèvremont, Alan Kania, Lola Torz, Christophe Lenglos, et al. "Estrous Cycle Modulation of Feeding and Relaxin-3/Rxfp3 mRNA Expression - Implications for Estradiol." Neuroendocrinology, December 17, 2020. http://dx.doi.org/10.1159/000513830.

Full text

Abstract:

Introduction: Food intake varies during the ovarian hormone/estrous cycle in humans and rodents, an effect mediated mainly by estradiol. A potential mediator of the central anorectic effects of estradiol is the neuropeptide relaxin-3 (RLN3) synthetised in the nucleus incertus (NI) and acting via the relaxin-family peptide-3 receptor (RXFP3). Methods: We investigated the relationship of RLN3/RXFP3 signaling and feeding behavior across the female rat estrous cycle. We used in situ hybridization to investigate expression patterns of Rln3 mRNA in NI and Rxfp3 mRNA in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamic area (LHA), medial preoptic area (MPA), and bed nucleus of the stria terminalis (BNST), across the estrous cycle. We identified expression of estrogen receptors in the NI using droplet digital polymerase-chain reaction and assessed the electrophysiological responsiveness of NI neurons to estradiol in brain slices. Results: Rln3 mRNA reached the lowest levels in the NI pars compacta during proestrus. Rxfp3 mRNA levels varied across the estrous cycle in a region-specific manner, with changes observed in the perifornical LHA, magnocellular PVN, dorsal BNST, and MPA, but not in the parvocellular PVN or lateral LHA. G protein-coupled estrogen receptor-1 (Gper1) mRNA was the most abundant estrogen receptor transcript in the NI. Estradiol inhibited 33% of type I NI neurons, including RLN3-positive cells. Conclusion: These findings demonstrate that the RLN3/RXFP3 system is modulated by the estrous cycle and although further studies are required to better elucidate the cellular and molecular mechanisms of estradiol signaling, current results implicate the involvement of RLN3/RXFP3 system in food intake fluctuations observed across the estrous cycle in female rats.

APA, Harvard, Vancouver, ISO, and other styles

49

Hauser, Frank, Thomas L. Koch, and Cornelis J. P. Grimmelikhuijzen. "Review: The evolution of peptidergic signaling in Cnidaria and Placozoa, including a comparison with Bilateria." Frontiers in Endocrinology 13 (September 23, 2022). http://dx.doi.org/10.3389/fendo.2022.973862.

Full text

Abstract:

Bilateria have bilateral symmetry and are subdivided into Deuterostomia (animals like vertebrates) and Protostomia (animals like insects and mollusks). Neuropeptides occur in both Proto- and Deuterostomia and they are frequently structurally related across these two lineages. For example, peptides belonging to the oxytocin/vasopressin family exist in both clades. The same is true for the G protein-coupled receptors (GPCRs) of these peptides. These observations suggest that these neuropeptides and their GPCRs were already present in the common ancestor of Proto- and Deuterostomia, which lived about 700 million years ago (MYA). Furthermore, neuropeptides and their GPCRs occur in two early-branching phyla that diverged before the emergence of Bilateria: Cnidaria (animals like corals and sea anemones), and Placozoa (small disk-like animals, feeding on algae). The sequences of these neuropeptides and their GPCRs, however, are not closely related to those from Bilateria. In addition, cnidarian neuropeptides and their receptors are not closely related to those from Placozoa. We propose that the divergence times between Cnidaria, Placozoa, and Bilateria might be too long for recognizing sequence identities. Leucine-rich repeats-containing GPCRs (LGRs) are a special class of GPCRs that are characterized by a long N-terminus containing 10-20 leucine-rich domains, which are used for ligand binding. Among the ligands for LGRs are dimeric glycoprotein hormones, and insulin-like peptides, such as relaxin. LGRs have been found not only in Proto- and Deuterostomia, but also in early emerging phyla, such as Cnidaria and Placozoa. Humans have eight LGRs. In our current review, we have revisited the annotations of LGRs from the sea anemone Nematostella vectensis and the placozoan Trichoplax adhaerens. We identified 13 sea anemone LGRs and no less than 46 LGRs from T. adhaerens. All eight human LGRs appear to have orthologues in sea anemones and placozoans. LGRs and their ligands, therefore, have a long evolutionary history, going back to the common ancestor of Cnidaria and Placozoa.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!