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Questions And Answer

• 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.;

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