Discovery
NMB was purified from the porcine spinal cord in 1983
as one of the peptides with a stimulant effect on rat uterus
contraction. NMB is structurally related to ranatensin, an
amphibian peptide belonging to the bombesin-like peptide family, which was purified in 1970 by Nakajima.
NMB cDNA was first isolated in the human and then
in the rat.
Structure
NMB was first identified as a decapeptide, but subsequently 30 (NMB-30) or 32 (NMB-32) forms were also
identified. The decapeptide (NMB) is also noted as
NMB23–32. The C-terminal residue of the peptide is
amidated. The amino acid sequences for the pig, human, and rat
NMB-32 are highly conserved, and only differ in 4 aa.
Their sequences of 11 aa from the C-terminus are
completely identical.
Gene, mRNA, and precursor
Human NMB is located on chromosome 15 (15q25.2)
and consists of three exons. Human NMB is encoded in
a 76-aa precursor protein (preproNMB), which consists
of a 24-aa signal peptide, a 32-aa mature peptide
(NMB-32), and a 17-aa C-terminal extended peptide.
The C-terminus of NMB-32 is flanked by a Gly-Lys-Lys
sequence, which is a target for proteolytic processing. Nmb in rats consists of three exons, and the intron-exon
border is well conserved in humans and rats. Rat preproNMB is 117 aa long, and its structure is similar to that
of human preproNMB. The difference exists in the length
of the extended peptide, which is 52 aa long instead of
17 aa, and the existence of a cleavage recognition site at
the C-terminus of the extended peptide.
Receptors
NMB binds the NMB-preferring receptor (NMBR,
also called BB1) with high affinity (Ki = 4 nM for rat
NMBR-transfected BALB3T3 cells), and also binds the
gastrin-releasing peptide-preferring receptor with
much lower affinity (Ki = 174 nM for mouse GRPRtransfected BALB3T3 cells). NMBR is a GPCR with seven-transmembrane domains. The TM5 segment is
shown to be critical for high affinity and selectivity for agonist binding. NMBR has been cloned in humans, rats,mice,
chicks, and frogs. Both human and rat NMBR cDNAs
encode a 390-aa residue protein, and the calculated Mr
is 43 kDa in rats. The sequence similarity of the NMBR
genes in mice, rats, and humans is 90%–97%. In rats, Nmbr
mRNA is detected notably in the olfactory regions, hippocampal formations, amygdala, thalamus, and central core,
and moderate expression is found in many other brain
regions. In the peripheral organs, strong expression is
found in the rat and mouse esophagus, and significant
levels of expression have been found by RT-PCR in the
intestines, testis, and uterus in mice.
Agonists and Antagonists
NMB is a naturally occurring agonist for NMBR. GRP
and NMC are naturally occurring agonists with lower
affinity for NMBR than GRPR. Labeled bombesin (BN)
analogs are useful for tumor imaging and BN receptor mediated cytotoxicity. PD168368 and PD176252 are antagonists with high
selectivity for the human NMBR.
Biological functions
NMB regulates smooth muscle contraction, exocrine
and endocrine secretions, body temperature, food intake,
energy homeostasis, grooming and scratching (itch perception), nociception, anxiety, sighing, locomotion, and
cell growth. The contractile effect
of NMB is found to be more potent than that of GRP in
the rat urinary bladder and esophagus.
Clinical implications
NMBR is expressed in various human cancers, including small cell lung carcinoma, nonsmall cell lung carcinoma, colon cancer, and various carcinoid tumors, and
NMB may have a growth effect. Because NMB has a regulatory function for TSH release, NMB could be implicated in human thyroid disorders.
Description
NMB is distributed in the central nervous system as well
as the gastrointestinal tract, and has many regulatory functions in physiology such as exocrine and endocrine secretions,
smooth muscle contraction, feeding, energy homeostasis,
body temperature, nociception, itch perception, anxiety,
sighing, and cell growth.
Uses
Neuromedin B, porcine is an endogenous activator for the NMBR (neuromedin B receptor).
General Description
Neuromedin B (NMB) belongs to the bombesin (BN)-like peptide family in mammals. It is located in the gastrointestinal tract and central nervous system.
Biochem/physiol Actions
Neuromedin B (NMB) exhibits its effects by binding to the cell surface receptors. It facilitates its action on several contractile organs including, the stomach, intestine, esophagus, gall bladder, urinary bladder, and uterus. It also plays a role in food intake, hypothermia, and thermoregulation. NMB is involved in exocrine and endocrine secretion of gastrin, insulin, cholecystokinin, enteroglucagon, and gastric inhibitory peptide. It also acts as an autocrine growth factor in non-small cell lung cancer.
