title: Increased feeding and body weight gain in rats after acute and chronic activation of RXFP3 by relaxin-3 and receptor-selective peptides:  functional and therapeutic implications.
abstract: This paper provides a review of the effects of relaxin-3 and structurally related analogues on food intake and related behaviours, in relation to hypothalamic neural networks and chemical messengers known to control feeding, metabolism and body weight, including other neuropeptides and hormones. Soon after relaxin-3 was discovered, pharmacological studies identified the ability of the native peptide to stimulate feeding acutely in adult rats. Although interpretation of these data was confounded by ligand cross-reactivity at relaxin-family peptide (RXFP) receptors, studies with relaxin-3 analogues selective for the native relaxin-3 receptor, RXFP3, confirmed that acute and chronic activation of RXFP3 increased feeding and weight gain, and produced changes in plasma leptin and insulin. These studies also identified the hypothalamus as a locus of action. Studies are now required to identify RXFP3-positive neuron populations involved in the effects of relaxin-3/RXFP3 signalling on metabolic and neuroendocrine homeostasis, and to determine whether peptide-based, nonpeptide-based or gene-based RXFP3 treatments can alter food intake and body weight in animal models of obesity and eating disorders, as a reflection of the therapeutic potential of this newly identified transmitter system.
authors.affiliation: Florey Neuroscience Institutes, The University of Melbourne, Victoria, Australia.
authors.forename: Despina E
authors.initials: DE
authors.lastname: Ganella
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ryan
authors.forename: Ross A D
authors.initials: RA
authors.lastname: Bathgate
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gundlach
mesh_terms: D000818:Animals; D019167:Appetite Stimulants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D001068:Feeding and Eating Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D008024:Ligands; D051379:Mice; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D012065:Relaxin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019167:Appetite Stimulants; D008024:Ligands; D009419:Nerve Tissue Proteins; D010455:Peptides; C466742:RLN3 protein, rat; C577472:RXFP3 protein, rat; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D012065:Relaxin