Neuromedin U: physiology, pharmacology and therapeutic potential

Neuromedin U (NmU), a multifunctional neuropeptide, belongs to a family of neuropeptides, the neuromedins. It is ubiquitously distributed with highest levels found in the gastrointestinal tract and pituitary. The conservation of structural elements of NmU across species, the widespread distribution of NmU and its receptors throughout the body point to a fundamental role in key physiological processes. Two G protein coupled receptors for NmU have been cloned NmU R1 and NmU R2. NmU R1 is expressed pre-dominantly in the periphery especially the gastrointestinal tract whereas NmU R2 is expressed pre-dominantly in the central nervous system. Current evidence suggests a role of NmU in pain, in regulation of feeding and energy homeostasis, stress, cancer, immune mediated inflammatory diseases like asthma, inflammatory diseases, maintaining the biological clock, in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract, and in the control of blood flow and blood pressure. With the development of drugs selectively acting on receptors and knockout animal models, exact pathophysiological roles of NmU will become clearer.