Neuromedin U receptor, type 1 (NeuromedU_rcpt_1)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Neuromedin U is a neuropeptide, first isolated from porcine spinal cord and expressed widely in the gastrointestinal, genitourinary and central nervous systems . Neuromedin U has potent contractile activity on smooth muscle and this activity is believed to reside within the C-terminal portion of the peptide, which is highly conserved between species. Other roles for the peptide include: regulation of blood flow and ion transport in the intestine, regulation of adrenocortical function and increased blood pressure . The roles of neuromedin U in the central nervous system are poorly understood, but may include: regulation of food intake, neuroendocrine control, modulation of dopamine actions and involvement in neuropsychiatric disorders. Two G protein-coupled receptor subtypes, with differing expression patterns, have been identified and shown to bind neuromedin U.

The neuromedin U type 1 receptor (NMU1) is expressed predominantly in the periphery, with highest levels in the gastrointestinal and urogenital systems, particularly in the testes . The receptor is also found in the kidney, pancreas, lung, trachea, adrenal cortex, liver and mammary glands . Within the small intestine and ileum, NMU1 is specifically expressed in goblet cells. In the central nervous system, the receptor is expressed only at much lower levels and has been detected most abundantly in the cerebellum, dorsal root ganglia, hippocampus and spinal cord. Binding of neuromedin U to the receptor results in phospholipase C activation and increased intracellular calcium concentrations through coupling to Gq proteins.