Neuromedin B (porcine)

Neuromedin B (NMB) is a member of Bombesin (BN)-like peptide family in mammals. Sequence: Gly-Asn-Leu-Trp-Ala-Thr-Gly-His-Phe-Met-NH2.

In Vitro:Potency to stimulate contraction of rat uterine smooth muscle, that is used as bioassay for isolation of Neuromedin B (NMB), is compared with Bombesin (BN). The relative potency, calculated on molar basis by taking BN as 100, is 48% for GRP and 4.9% for NMB. NMB also has contractile activity on rat stomach strip, but the potency (ratio of peptide concentration required to elicit 50% maximum response; EC50) is only 5% of BN (EC50 of BN/EC50 of NMB) and about 10% of GRP (EC50 of GRP/ EC50 of NMB)[1].

In Vivo:Potencies of NMB and GRP for smooth muscle contraction of fundus in wild-type and NMB-R-deficient mice with ED50 of 14.4±2.3 (n=8) and 10.9±2.3 (n=8) in wild-type mice and NMB-R-deficient mice, respectively[1].

References:
[1]. Ohki-Hamazaki H. Neuromedin B. Prog Neurobiol. 2000 Oct;62(3):297-312.

Neuromedin B-32 and B-30: two "big" neuromedin B identified in porcine brain and spinal cord.[Pubmed:4026853]

Biochem Biophys Res Commun. 1985 Jul 31;130(2):685-91.

In mammalian spinal cord, we have previously discovered "neuromedin B", whose structure is closely related to amphibian bombesin. By utilizing a specific radioimmunoassay for neuromedin B, we have isolated two novel "big" neuromedin B, designated neuromedin B-32 and B-30, from pig brain and spinal cord, both of which were identified as N-terminally extended forms of neuromedin B. The amino acid sequence of neuromedin B-32 was determined to be: Ala-Pro-Leu-Ser-Trp-Asp-Leu-Pro-Glu-Pro- Arg-Ser-Arg-Ala-Gly-Lys-Ile-Arg-Val-His-Pro-Arg-Gly-Asn-Leu-Trp-Ala- Thr-Gly-His-Phe-Met-NH2, while neuromedin B-30 was found to be an N-terminal two amino acids deleted form of neuromedin B-32. Isolation of a family comprising neuromedin B, B-30 and B-32 is indicative of their biosynthetic relationship.

Neuromedin B: a novel bombesin-like peptide identified in porcine spinal cord.[Pubmed:6882442]

Biochem Biophys Res Commun. 1983 Jul 29;114(2):541-8.

In our survey for unknown neuropeptides in porcine spinal cord, we have purified a novel decapeptide that exhibits a potent stimulant effect on the smooth muscle preparation of rat uterus. By microsequencing and synthesis, the peptide has been identified as Gly-Asn-Leu-Trp-Ala-Thr-Gly-His-Phe-Met-NH2. The peptide is found to have a surprising sequence homology to amphibian bombesins, and to display a potent contractile activity of rat uterus in the characteristic manner of the known bombesins. These facts strongly suggest that the peptide may be involved in the neural communication system of mammals as a neuromediator or hormone. Thus, we propose the name "neuromedin B" for the peptide.

Neuromedin B.[Pubmed:10840151]

Prog Neurobiol. 2000 Oct;62(3):297-312.

Neuromedin B (NMB) is one of the bombesin (BN)-related peptides in mammals. It was originally purified from pig spinal cords, and it has been shown to be present in central nervous system as well as in gastrointestinal tract. BN and its related peptides have various physiological effects. These include regulation of exocrine and endocrine secretions, smooth muscle contraction, feeding, blood pressure, blood glucose, body temperature and cell growth. NMB exerts its effect by binding to the cell surface receptor. A high affinity receptor, NMB receptor (NMB-R) has been identified. This is a G-protein coupled receptor with seven membrane-spanning regions. Upon agonist binding, several intracellular signaling cascades including phospholipase activation, calcium mobilization and protein kinase C (PKC) activation lead to expression of several genes, DNA synthesis or cellular effects such as secretion. Existence of NMB-R has been demonstrated in several brain regions, notably in olfactory and thalamic regions, and in gastrointestinal tracts. Recent analysis using NMB-R-deficient mice, generated by gene-targeting technique, enables to distinguish functional properties of NMB-R from GRP-R. In this review, molecular characterization, anatomical distribution and pharmacological properties of NMB and NMB-R will be presented. Moreover, physiological roles of NMB and its receptor demonstrated by the analysis of NMB-R-deficient mice will be reported. Comparison with GRP/GRP-R system will provide important information about BN-like peptide systems in mammals.

Four amino acid residues are critical for high affinity binding of neuromedin B to the neuromedin B receptor.[Pubmed:9632639]

J Biol Chem. 1998 Jun 26;273(26):15927-32.

Three mammalian bombesin receptor subtypes have been characterized: the gastrin-releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and bombesin receptor subtype 3 (BRS-3). In a previous report we identified four amino acids that are critical for high affinity binding of bombesin and gastrin-releasing peptide (GRP) to the GRP-R. These four amino acids are conserved in all species variants of the GRP-R and NMB-R which bind bombesin with high affinity, but they are diverged in BRS-3, the bombesin receptor subtype that binds bombesin with much lower affinity. Substituting these four divergent amino acids in BRS-3 for the conserved amino acids in either GRP-R or NMB-R increased the affinity of the mutated BRS-3 (4DeltaBRS-3) for bombesin compared with wild-type BRS-3. We hypothesized that the same four amino acids might be critical for high affinity NMB binding to the NMB-R. In this study we confirm this hypothesis by showing that the affinity of NMB is increased in a mutant BRS-3 receptor (4DeltaBRS-3) that contains these four substitutions resulting in an affinity that is close to the affinity of wild-type NMB-R for NMB. In contrast, these four amino acid substitutions in BRS-3 did not result in the formation of a high affinity binding site for the recently described non-peptide NMB-R antagonist PD168368.