Disease relevance of Nmb

• Activation of neuromedin B-preferring bombesin receptors on rat glioblastoma C-6 cells increases cellular Ca2+ and phosphoinositides [1].
• The distributions of three novel peptides, 7B2, neuromedin B, and neuromedin U, in rat, mouse, and human pituitaries, rat hypothalamus, and 30 human pituitary tumors were investigated with immunocytochemistry [2].
• Bombesin-like peptides including neuromedin B have been proposed as autocrine or paracrine growth factors for carcinomas [3].

High impact information on Nmb

• Relative binding affinity of GRP analogues was in the order of GRP (14-27) greater than neuromedin C greater than or equal to BBS greater than or equal to GRP (1-27) greater than neuromedin B (for the later, P greater than 0.05 versus other peptides) [4].
• The receptor for neuromedin B (NMB-R), a mammalian bombesin-related peptide, is widely distributed in the central nervous system and gastrointestinal tract [5].
• GRP had the same effects as bombesin, whereas neither NMB nor a synthetic bombesin receptor type 3 ligand had any effect [6].
• Neuromedin B (NMB) receptor-null and bombesin receptor subtype 3-null mice had the same responses as their wild-type littermates [6].
• The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells [7].

Chemical compound and disease context of Nmb

• NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells [8].
• These results demonstrate that the rat glioblastoma cell line C-6 possesses functional NMB-preferring Bn receptors, and agonist occupation activates phospholipase C, thus increasing cytosolic Ca2+ and inositol phosphate formation [1].

Biological context of Nmb

• Neuromedin B receptors retain functional expression when transfected into BALB 3T3 fibroblasts: analysis of binding, kinetics, stoichiometry, modulation by guanine nucleotide-binding proteins, and signal transduction and comparison with natively expressed receptors [9].
• The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52% [8].
• This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A) [10].
• GRP increased incorporation of [3H]thymidine and [3H]choline in explants, whereas NMB induced cell proliferation and Leu8-phyllolitorin yielded variable results [11].
• Also, neuromedin-B is potentially a bifunctional regulator of cell growth [3].

Anatomical context of Nmb

• Neuromedin B is degraded by a similar pathway in a mouse neuronal cell line and also in cultured human fibroblasts [12].
• The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system [9].
• Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse, and human pituitary, in rat hypothalamus, and in 30 human pituitary and extrapituitary tumors [2].
• The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK) [8].
• Kuwanon H was one order of magnitude less potent for inhibiting [125I]bombesin binding to neuromedin B (NMB)-preferring receptors in rat esophagus membranes [13].

Associations of Nmb with chemical compounds

• NMB mobilized intracellular Ca2+ in both cell systems, and the dose-response curves were superimposible (EC50 for transfected, 0.10 +/- 0.08 nM; C6, 0.11 +/- 0.02 nM) [9].
• In both cell systems, NMB increased inositol monophosphate, inositol bisphosphate, and inositol trisphosphate in a time-dependent fashion [9].
• However, tyrphostin A25 did not inhibit NMB-stimulated increases in [3H]inositol phosphates [8].
• For Bn receptor agonists the relative potencies were: NMB (1.7 nM) approximately equal to litorin (3 nM) greater than ranatensin (8 nM) greater than Bn (19 nM) greater than neuromedin C (NMC) (210 nM) greater than GRP (500 nM) [1].
• TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB [8].

Regulatory relationships of Nmb

• Complete desensitization of gastrin releasing peptide-evoked responses in oocytes expressing esophagus mRNA does not abolish neuromedin B-evoked responses [14].

Other interactions of Nmb

• Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity [15].
• In neuromedin B receptor transfected BALB cells, this ligand and 125I-[D-Tyr0]neuromedin B, the generally used neuromedin B receptor ligand, gave similar results for receptor number, neuromedin B affinity or the unlabeled ligand affinity [16].
• Thyrotropin secretagogues reduce rat pituitary neuromedin B, a local thyrotropin release inhibitor [17].
• PD168368 inhibited the ability of 100 nM neuromedin B to cause elevation of c-fos mRNA [18].
• Because neuromedin B is a G-protein coupled serpentine receptor, the effects of neuromedin B antagonists on second messenger production and proliferation were investigated [18].

Analytical, diagnostic and therapeutic context of Nmb

• Neuromedin B immunoreactivity was found in normal rat and mouse thyrotropes and weakly in "thyroidectomy" cells in hypothyroid rats, in which extractable pituitary neuromedin B was significantly depleted (thyroidectomized, 87.0 +/- 14.0; methimazole-treated, 82.0 +/- 11.4; control, 230.7 +/- 25.6 fmol/gland) [2].

References