PMID- 26147879
OWN - NLM
STAT- MEDLINE
DCOM- 20160602
LR  - 20220309
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 100
IP  - 9
DP  - 2015 Sep
TI  - Involvement of central relaxin-3 signalling in sodium (salt) appetite.
PG  - 1064-72
LID - 10.1113/EP085349 [doi]
AB  - What is the central question of this study? Sodium appetite is controlled by 
      conserved neuronal transmitter-receptor systems. Here, we tested the contribution 
      made by relaxin family peptide 3 receptor (RXFP3), the cognate G-protein-coupled 
      receptor for the neuropeptide relaxin-3. What is the main finding and its 
      importance? Intracerebroventricular infusion of an RXFP3 antagonist reduced in a 
      dose-dependent manner the volume of 0.3 m NaCl consumed by sodium-depleted 
      C57Bl/6J (wild-type) mice. This effect was absent in sodium-depleted Rxfp3 
      knockout mice, and RXFP3 antagonist infusion did not alter water consumption in 
      wild-type mice subjected to multiple thirst tests, indicating both the 
      pharmacological and the physiological specificity of observed effects. Our 
      findings identify endogenous relaxin-3-RXFP3 signalling as a modulator of sodium 
      appetite. Overconsumption of highly salted foods is common in Western diets and 
      contributes significantly to metabolic disorders such as hypertension, renal 
      dysfunction and diabetes. Sodium appetite, or the desire of terrestrial animals 
      to seek and consume sodium-containing salts, is a behaviour mediated by a set of 
      evolutionarily conserved neuronal systems. In these studies, we tested whether 
      this instinctive behavioural drive is influenced by the G-protein-coupled relaxin 
      family peptide 3 receptor (RXFP3), the cognate receptor for the neuropeptide 
      relaxin-3, because relaxin-3-RXFP3 signalling can modulate arousal, motivation 
      and ingestive behaviours. Intracerebroventricular (i.c.v.) infusion of the 
      selective RXFP3 antagonist, R3(B1-22)R, reduced in a dose-dependent manner the 
      volume of 0.3 m NaCl solution consumed when offered to sodium-depleted C57Bl/6J 
      wild-type mice, relative to vehicle-treated control animals. Notably, i.c.v. 
      R3(B1-22)R infusion did not alter 0.3 m NaCl consumption relative to vehicle in 
      sodium-depleted Rxfp3 knockout mice, confirming the pharmacological specificity 
      of this effect. Furthermore, i.c.v. R3(B1-22)R did not alter the volume of water 
      consumed by wild-type mice in three tests where water drinking was the normal 
      physiological response, suggesting that the ability of R3(B1-22)R to reduce 
      activated salt appetite is specific and not due to a generalized reduction in 
      drinking behaviour. These findings identify, for the first time, that endogenous 
      relaxin-3-RXFP3 signalling is a powerful mediator of salt appetite in mice and 
      further elucidate the functional role of the relaxin-3-RXFP3 system in the 
      integrative control of motivated behaviours.
CI  - (c) 2015 The Authors. Experimental Physiology (c) 2015 The Physiological Society.
FAU - Smith, Craig M
AU  - Smith CM
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
AD  - Florey Department of Neuroscience and Mental Health, The University of Melbourne, 
      Victoria, Australia.
FAU - Walker, Lesley L
AU  - Walker LL
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
FAU - Chua, Berenice E
AU  - Chua BE
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
FAU - McKinley, Michael J
AU  - McKinley MJ
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
AD  - Department of Physiology, The University of Melbourne, Victoria, Australia.
FAU - Gundlach, Andrew L
AU  - Gundlach AL
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
AD  - Florey Department of Neuroscience and Mental Health, The University of Melbourne, 
      Victoria, Australia.
AD  - Department of Anatomy and Neuroscience, The University of Melbourne, Victoria, 
      Australia.
FAU - Denton, Derek A
AU  - Denton DA
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
AD  - Office of the Dean, Faculty of Medicine, Dentistry and Health Sciences, The 
      University of Melbourne, Victoria, Australia.
AD  - Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
FAU - Lawrence, Andrew J
AU  - Lawrence AJ
AD  - The Florey Institute of Neuroscience and Mental Health, The University of 
      Melbourne, Victoria, Australia.
AD  - Florey Department of Neuroscience and Mental Health, The University of Melbourne, 
      Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150727
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Neuropeptides)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (SALPR protein, mouse)
RN  - 0 (Sodium Chloride, Dietary)
RN  - 0 (relaxin-3 protein, mouse)
RN  - 9002-69-1 (Relaxin)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
MH  - Animals
MH  - Appetite/*physiology
MH  - Arousal/physiology
MH  - Drinking Behavior/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuropeptides/metabolism
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Relaxin/*metabolism
MH  - Signal Transduction/physiology
MH  - Sodium/*metabolism
MH  - Sodium Chloride, Dietary/*metabolism
EDAT- 2015/07/07 06:00
MHDA- 2016/06/03 06:00
CRDT- 2015/07/07 06:00
PHST- 2015/05/26 00:00 [received]
PHST- 2015/06/30 00:00 [accepted]
PHST- 2015/07/07 06:00 [entrez]
PHST- 2015/07/07 06:00 [pubmed]
PHST- 2016/06/03 06:00 [medline]
AID - 10.1113/EP085349 [doi]
PST - ppublish
SO  - Exp Physiol. 2015 Sep;100(9):1064-72. doi: 10.1113/EP085349. Epub 2015 Jul 27.