| A 20aa peptide within the extracellular, N-terminal domain of rat, and a 20-aa peptide mapping at the cytoplasmic, C-terminal domain of human NMUR1. The neuromedins (Nm) are a family of bioactive peptides best known for their roles in smooth muscle contraction. Nm family of bioactive peptides include: Bombesin-like (NmB, NmC), kassinin-like (NmL and NmK or neurokinins A and B), neurotensin-like (NmN), and neuromedin U (NmU, for its ability to stimulate uterine muscle contraction). Besides its roles in smooth muscle contraction (human ileum, urinary bladder, rat stomach etc), NmU has also been implicated in hypertension, blood flow in intestine, and neurotransmission. Recently two structurally related, orphan G-protein coupled receptors, termed NMUR1 (GPCR66/FM-3/SNORF62) and NMUR2 (TGR-1/FM-4/SNORF72), have been identified as cognate receptors of NmU. NMU receptors display a typical 7 TM domains with extracellular N-terminus and intracellular C-terminus. The human NMUR1 (rat 402 aa, mouse, 405 aa, human 403 aa, chromosome 2, 70-80% interspecies homology) orphan GPCR66 was originally identified by similarity to mouse orthologue FM-3. NMUR1 has moderate sequence homology with neurotensin (NT), and growth hormone secretagogue (GHS, Ghrelin) receptors. NMUR1 is specifically activated by the three peptides (NmU-25, NmU23, and NmU-8) with more or less the same potency. Calcium mobilization assay suggests that NMUR1 is coupled to G-protein of the Gq/11 subfamily. It is highly expressed in rat small intestine and lung. In human, highest expression was found in intestine adipose tissue, with moderate levels of expression in the intestine, lymphocytes, stomach, pancreas, bone marrow, and spleen, and low levels in most other tissues including brain. |
