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Relaxin family peptides and receptors in mammalian brain
journal contribution
posted on 2009-04-01, 00:00 authored by A L Gundlach, S Ma, Q Sang, P-J Shen, L Piccenna, K Sedaghat, Craig SmithCraig Smith, R A D Bathgate, A J Lawrence, G W Tregear, J D Wade, D I Finkelstein, P Bonaventure, C Liu, T W Lovenberg, S W SuttonAs a foundation for regulatory and functional studies of central relaxin family peptide receptor systems, we are mapping the distribution of the different receptors in the brain of rat, mouse, and nonhuman primates, attempting to identify the nature of the receptor-positive neurons in key circuits and establish the complementary distribution of the respective ligands in these species. Here we review progress in mapping RXFP1, RXFP2, and RXFP3 (mRNAs and proteins) and their respective ligands and discuss some of the putative functions for these peptides and receptors that are being explored using receptor-selective agonist and antagonist peptides and receptor and peptide gene deletion mouse strains. Comparative studies reveal an association of RXFP1 and RXFP2 with excitatory neurons but a differential regional or cellular distribution, in contrast to the association of RXFP3 with inhibitory neurons. These studies also reveal differences in the distribution of RXFP1 and RXFP2 in rat and mouse brain, whereas the distribution of RXFP3 is more conserved across these species. Enrichment of RXFP1/2/3 in olfactory, cortical, thalamic, limbic, hypothalamic, midbrain, and pontine circuits suggests a diverse range of modulatory actions for these receptors. For example, experimental evidence in the rat reveals that RXFP1 activation in the amygdala inhibits memory consolidation, RXFP2 activation in striatum produces sniffing behavior, and RXFP3 modulation has effects on feeding and metabolism, the activity of the septohippocampal pathway, and spatial memory. Further studies are now required to reveal additional details of these and other functions linked to relaxin family peptide receptor signaling in mammalian brain and the precise mechanisms involved.
History
Journal
Ann N Y Acad SciVolume
1160Pagination
226 - 235Publisher
Wiley-Blackwell Publishing, Inc.Location
United StatesPublisher DOI
eISSN
1749-6632Language
engPublication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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AnimalsBrainCerebral CortexHumansReceptors, PeptideRelaxinrelaxin-3insulin-like peptide-3insulin-likepeptide-3RXFP1\/2\/3LGR7\/8GPCR135\/142ratmouseprimatein situ hybridizationhybridizationimmunohistochemistryradioligand binding sitessomatosensorylimbicneuroendocrine systemscognitionstressScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyEndocrinology & MetabolismMultidisciplinary SciencesPhysiologyScience & Technology - Other Topicsrelaxin and relaxin-3rat mouse and primatesomatosensory, limbic, and neuroendocrine systemsINSULIN-LIKE FACTOR-3MESSENGER-RNARAT-BRAINNUCLEUS INCERTUSCHIMERIC PEPTIDEBINDING-SITESKNOCKOUT MICEMOUSE-BRAININ-VITROPROTEIN
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