Abstract
The discovery of neuropeptides provides insights into the regulation of physiological processes. The precursor for the neuropeptide neuromedin U contains multiple consensus sequences for proteolytic processing, suggesting that this precursor might generate additional peptides. We performed immunoaffinity chromatography of rat brain extracts and consequently identified such a product, which we designated neuromedin U precursor-related peptide (NURP). In rat brain, NURP was present as two mature peptides of 33 and 36 residues. Radioimmunoassays revealed NURP immunoreactivity in the pituitary, small intestine, and brain of rats, with the most intense reactivity in the pituitary. Intracerebroventricular administration of NURP to both male and female rats robustly increased plasma concentrations of prolactin but not of other anterior pituitary hormones. In contrast, NURP failed to stimulate prolactin release from dispersed anterior pituitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sulpiride, intracerebroventricular administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data suggest that NURP induces prolactin release by acting indirectly on the pituitary; dopamine from the hypothalamus, which inhibits prolactin release, may be involved in this activity of NURP.
Highlights
Neuropeptides and peptide hormones are major signalling molecules responsible for cell-to-cell communication and play pivotal roles in regulating a variety of physiological phenomena
Four potential proteolytic cleavage sites are conserved in the Neuromedin U (NMU) precursors from mammals to fish (Supplementary Fig. S1) and in the mammalian neuromedin S (NMS) precursors (Fig. 1a)[14]
We biochemically identified neuromedin U precursor-related peptide (NURP), a neuropeptide produced from the same precursor as NMU
Summary
Neuropeptides and peptide hormones are major signalling molecules responsible for cell-to-cell communication and play pivotal roles in regulating a variety of physiological phenomena. Many neuropeptides and peptide hormones have been discovered by purification from tissue extracts that display a biological activity of interest, several have been identified on the basis of common structural features, including consensus sequences for processing of the precursor[2,3,4,5]. Intracerebroventricular (ICV) administration of NMU causes several biological responses, including suppression of feeding and increases in energy expenditure[7, 9, 12, 13]. In another previous study, we identified the novel 36-residue neuropeptide neuromedin S (NMS), which activates both NMUR1 and NMUR2 in a cell-based assay in a manner similar to NMU14. Other novel neuropeptides may be produced from the NMU and NMS precursors by proteolytic cleavage at both the first and second sites, but biochemical evidence for such putative neuropeptides is unavailable currently
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