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Metabolic and neuroendocrine responses to RXFP3 modulation in the central nervous system
conference contribution
posted on 2009-04-01, 00:00 authored by S W Sutton, J Shelton, Craig SmithCraig Smith, J Williams, S Yun, T Motley, C Kuei, P Bonaventure, A Gundlach, C Liu, T LovenbergNeuroanatomical studies have shown relaxin-3 neurons, primarily found in the rodent nucleus incertus (NI), project widely into a large number of areas expressing the relaxin-3 receptor (RXFP3), and these data suggest relaxin-3/RXFP3 signaling modulates sensory, emotional, and neuroendocrine processing. The similar distribution of this receptor-ligand pair in the rat, mouse, and monkey brain suggests that experimental findings obtained in lower species will translate to higher species. A role for relaxin-3 and RXFP3 in modulating stress responses is strongly suggested by the expression of corticotropin-releasing factor R1 (CRF-R1) by NI cells, increased relaxin-3 expression in the NI after stress or CRF injection, and hormonal responses to intracerebroventricular (i.c.v.) relaxin-3 injection. Recent data are consistent with a further role for this ligand-receptor pair in modulating memory. In addition, relaxin-3 has been reported to modulate feeding and body weight control. Acute or chronic central (i.c.v. or intraparaventricular) injections of relaxin-3 have shown a consistent stimulatory effect on food consumption while relaxin was inactive, suggesting the phagic effect of relaxin-3 is mediated by RXFP3. We have confirmed the role of RXFP3 in modulating feeding and body weight by using a selective RXFP3 agonist (R3/I5) and antagonist [R3(Delta23-27)R/I5], collecting feeding, body weight, hormone, and body composition data. In addition, we have preliminary body weight and magnetic resonance imaging data from relaxin-3 knockout mice, which on a 129S5:B6 background are smaller and leaner than congenic controls. These data suggest relaxin-3, acting through RXFP3, is involved in coordinating stress, learning and memory, and feeding responses as predicted on the basis of neuroanatomy.
History
Event
International conference on relaxin and related peptides. Conference (5th : 2008 : Maui, Hawaii)Volume
1160Series
International conference on relaxin and related peptidesPagination
242 - 249Publisher
WileyLocation
Maui, HawaiiPlace of publication
Medford, Mass.Publisher DOI
Start date
2008-05-18End date
2008-05-23ISSN
0077-8923eISSN
1749-6632ISBN-13
9781573317214Language
engPublication classification
E1.1 Full written paper - refereedCopyright notice
2009, New York Academy of SciencesEditor/Contributor(s)
G Bryant-Greenwood, C Bagnell, R Bathgate, O SherwoodTitle of proceedings
Proceedings of the International Conference on Relaxin and Related Peptides 2008Usage metrics
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No categories selectedKeywords
RXFP3GPCR135relaxin-3H3 relaxinR3\/I5agonistantagonistfeedingAnimal FeedAnimalsBody WeightCentral Nervous SystemHumansMiceNeurosecretory SystemsRatsReceptors, G-Protein-CoupledRelaxinScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyEndocrinology & MetabolismMultidisciplinary SciencesPhysiologyScience & Technology - Other TopicsR3\/15COUPLED RECEPTOR SALPRCHIMERIC PEPTIDEMOUSE-BRAINGPCR142LIGANDIDENTIFICATIONBINDINGFAMILY
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