Neuromedin s is a novel anorexigenic hormone.
A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for alpha-MSH) and alpha-helical corticotropin-releasing factor-(9-41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.
Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2155, Japan.
Takanori
T
Ida
Kenji
K
Mori
Mikiya
M
Miyazato
Yutaka
Y
Egi
Shinsuke
S
Abe
Keiko
K
Nakahara
Masugi
M
Nishihara
Kenji
K
Kangawa
Noboru
N
Murakami
D000818:Animals; D001067:Appetite Depressants; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002149:Energy Intake; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology
D001067:Appetite Depressants; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; C497950:neuromedin S; D011333:Pro-Opiomelanocortin