|
|
      |
|
|
|
| GENTAUR • Belgium : + 32 2 7325688 • France : 01 43250150 • Italy : 02 36006593 • Germany : +49 241 6085 13140 | |
| |||||
|
|
Neuromedin U (NmU) and Neuromedin
Receptors 1 (NmUR1/GPR66/FM-3)
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). Two molecular forms of NmU, NmU-25 and its cleavage product (NmU-8) were initially isolated in 1985 from porcine spinal cord and then found in variety of mammals, birds, and reptile. NmU-like immunoreactivity has been detected in mammalian brain, GI-tracts of various species, and in the thyroid and endocrine cells of pituitary glands. 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. Recent identification of two structurally related, orphan G-protein coupled receptors, termed NMUR1 (GPCR66/FM-3/SNORF62) and NMUR2 (TGR-1/FM-4/SNORF72), as cognate receptors of NmU will help understand the physiological roles of NmU at the cellular and molecular levels. NMU receptors display a typical 7 TM domains with extracellular N-terminus and intracellular C-terminus. NmU is synthesized from a large precursor peptide and cleaved into 25-aa (human NmU, 25 aa; rat NmU, 23 aa; porcine NmU, 25 aa) and 8-aa (Nmu-8; 18-25) biologically active peptides. NMU peptides from various species share the greatest homology in the their C-terminal regions, which is also critical in biological activity. NMU is present in nerves throughout the GI-tracts, corticotrophs within the anterior and lobe of rat and human pituitary glands, parafollicular cells of in rat thyroid gland, and in various regions of brain (spinal cord, hypothalamus, substantia nigra, hippocampus, amygdala). Low levels of NmU are also found in human adipose tissue, lymphocytes, and spleen. 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. NMUR1 is found at low levels in uterus, where NmU has
robust contractile activity and strong specific NmU binding sites have been
found in uterus suggesting the presence of another NmU receptor. A novel GPCR,
termed NMUR2
(FM-4/TGR-1/SNORF72) has been identified as the 2nd receptor for NmU. NMUR2 (rat
395 aa; human 415 aa; chromosome 5q31.1; ~78% homology) has approx 50% homology
with NMUR1. NMUR2 also couples to Gq in the signal transduction pathway. Unlike
NMUR1, NMUR2 was primarily expressed in the rat uterus, and brain. Moderate to
low level of expression was found in rat lung, ovary, and GI-tract. In human,
NMUR2 has highest expression in testing and brain. Moderate expression was also
detected in kidney, lung, and thyroid.
m=mouse; r=rat; h=human;
b=bovine; d=dog; ~CT or ~NT=near C or N-terminus. EC=Extracellular;
CP=Cytoplasmic domain; Control peptides (unconjugated,
free, antigenic peptides), because of their small
size, are not recommended for Western. They should be
used in ELISA/antibody blocking studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
© 2005 GENTAUR bvba |
