Abstract
We reviewed neuromedin U (NMU) and neuromedin S (NMS) involvement in the regulation of the hypothalamo–pituitary–adrenal (HPA) axis function. NMU and NMS are structurally related and highly conserved neuropeptides. They exert biological effects via two GPCR receptors designated as NMUR1 and NMUR2 which show differential expression. NMUR1 is expressed predominantly at the periphery, while NMUR2 in the central nervous system. Elements of the NMU/NMS and their receptors network are also expressed in the HPA axis and progress in molecular biology techniques provided new information on their actions within this system. Several lines of evidence suggest that within the HPA axis NMU and NMS act at both hypothalamic and adrenal levels. Moreover, new data suggest that NMU and NMS are involved in central and peripheral control of the stress response.
Highlights
In search for new biologically active peptides, the group of Minamino, Kangawa, and Matsuo in the 1980s isolated numerous small neuropeptides from porcine spinal cord
All of them exerted potent smooth-muscle stimulating activity. These short peptides have been named neuromedins (Minamino et al, 1985). Their sequences and biological activities are similar to some known neuropeptides and they are commonly divided into four groups: Identification of specific neuromedin U (NMU) receptors (NMUR1 and neuromedin U receptor 2 (NMUR2)) and its anorexigenic action have enhanced interest in physiological role of NMU and neuromedin S (NMS) (Howard et al, 2000; Ida et al, 2005)
We suggested that the medullary mediator of NMU action on adrenal cortex may activate 18-hydroxylation and aldosterone synthase activity
Summary
In search for new biologically active peptides, the group of Minamino, Kangawa, and Matsuo in the 1980s isolated numerous small neuropeptides from porcine spinal cord. Detailed studies on rat adrenal gland revealed very low expression of NMU and NMS genes at mRNA levels (Rucinski et al, 2007). Of mode of administration (icv, iPVN, or sc) NMU activates CRH containing neurons and stimulates CRH secretion, which in turn triggers pituitary ACTH and adrenal corticosterone/cortisol secretion. In this regard it is not astonishing that NMU and NMS are involved in central and peripheral control of the stress response. Recent development of a metabolically stable analog of NMU, based on derivatization of the native peptide with high molecular weight poly(ethylene) glycol (PEG) (“PEGylation”) may be helpful in these attempts (Ingallinella et al, 2012)
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