Functional analysis and search for novel bioactive peptides associated with regulation of feeding behavior and energy balance.

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In this study, we found a novel agonist activity for neuromedin U type 2 receptor(NMU2R) in rat brain extract. This activity was eluted in fractions with a larger molecular mass by gel filtration compared to rat NMU. As a result of purification and structural determination, a novel 36-residue peptide was identified and designated as neuromedin S(NMS), because it is specifically expressed in the suprachiasmatic nuclei(SCN) of the hypothalamus. The C-terminal amidated seven-residue sequence of NMS is identical to that of NMU. Pharmacological characterization indicated that NMS and NMU share quite similar potency and efficacy for both NMU1R and NMU2R. In rat brain, NMS mRNA was specifically expressed in the SCN, which is the site of the master circadian pacemaker. NMS expression in the SCN showed a diurnal peak under light/dark cycling, but remained stable under constant darkness. Intracerebroventricular(ICV) administration of NMS in rats induced nonphotic type phase shifts in the circadi … More an rhythm of locomotor activity. On the other hand, low level expression of NMS mRNA was also found in the paraventricular nuclei of the hypothalamus, which is closely implicated in the regulation of the feeding. ICV-administered NMS induced more potent suppression of feeding than NMU. These findings suggest that NMS is implicated in the regulation of circadian rhythm and feeding behaviour(1).NMU is a potent endogenous anorectic and catabolic signaling molecule in manmalian, Following our recent observations of inactivity and slowed movement in neuromedin U knockout(NMU KO) mice, we compared nociceptive reflexes and environmental adaptation in NMU KO and wild-type mice. The results suggest that endogenous NMU may be involved in reflexes and adaptation to environmental stimuli (2). We also elucidated the central role of NMU in avian species using Japanese quail. Endogenous NMU plays an important role in the regulation of food intake and body temperature in avian species as well as mammalian (3).Ghrelin, a novel peptide purified from stomach in our laboratory, and cholecystokinin(CCK) are gastrointestinal hormones regulating feeding via the vagal afferent nerve. We examined the functional relationship between ghrelin and CCK in the short-term regulation of food intake using rats disrupted CCK type A receptor and electrophysiological study. The results indicate that the vagus nerve plays a crucial role in determining peripheral energy balance. The efficiency of ghrelin and CCK signal transduction may depend on the balance of their respective plasma concentration and/or on interactions between GHS-R and CCK-AR (4). Less