[The discovery of neuromedin U and its pivotal role in the central regulation of energy homeostasis].
Neuromedin U (NMU) is a structurally highly conserved neuropeptide and has been paired with the G-protein-coupled receptors (GPCRs) NMUR1 and NMUR2, which were formerly classified in the orphan receptor family. Activation of the G protein Gq/11 subunit causes a pertussis toxin (PTX)-insensitive activation of both phospholipase C and mitogen-activated protein kinase (MAP), and activation of the Go subunit causes a PTX-sensitive inhibition of adenyl cyclase. Additionally, NMU selectively inhibits L-type high-voltage-gated Ca2+ channels in mouse hippocampus, as well as low-voltage-activated T-type Ca2+ channels in mouse dorsal root ganglia (DRG). NMU peptide and its receptors are predominantly expressed in the gastrointestinal tract and specific structures within the brain, reflecting its major role in the regulation of energy homeostasis. A novel neuropeptide, neuromedin S (NMS), is structurally related to NMU. They share a C-terminal core structure and both have been implicated in the regulation of food intake, as well as the circadian rhythms. The acute anorectic and weight-reducing effects of NMU and NMS are mediated by NMUR2. This suggests that NMUR2-selective agonists may be useful for the treatment of obesity.
Pracownia Biotechnologii i Genomiki, Katedra Hodowli Trzody Chlewnej i Małych Przeżuwaczy Wydziału Hodowli i Biologii Zwierząt UR w Krakowie. k.kirsz.ur@gmail.com
Katarzyna
K
Kirsz
Dorota A
DA
Zięba
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002940:Circadian Rhythm / Q000502:physiology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009479:Neuropeptides / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D015431:Weight Loss
D020746:Calcium Channels, L-Type; D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C497950:neuromedin S; C082444:neuromedin U receptor; C056900:neuromedin U; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11