Disease relevance of Nmbr

• In the present study we have investigated Bn receptors on the rat glioblastoma cell line C-6, reported to contain mRNA of the NMB receptor subtype [1].

Psychiatry related information on Nmbr

• These results suggest that the NMB-R has an essential role in thermoregulation, but not for smooth muscle contraction of the fundus or for the suppression of feeding behavior [2].
• An administration of [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN (antagonizes GRP-R>neuromedin B receptor (NMB-R)) impaired the performance of inhibitory avoidance learning in all doses (16, 32, 64 nmol/kg) [3].
• In the current study, we assessed the effects of stress on maternal behavior in female NMB-R-deficient mice [4].

High impact information on Nmbr

• We describe the structure and expression of a cloned NMB-preferring bombesin receptor (NMB-R) with properties distinct from a GRP-preferring bombesin receptor (GRP-R) reported previously [5].
• Compensation for NMB-R deficiency by overexpression of GRP-R and/or BRS-3 was not detected [2].
• Administration of GRP but not NMB suppressed glucose intake in both normal and NMB-R-deficient mice [2].
• In contrast, fundic smooth muscle contraction on stimulation with NMB or GRP was normal in NMB-R-deficient mice [2].
• In addition, the behavioral phenotypes of GRP-R-deficient mice were not observed in NMB-R-deficient mice [2].

Biological context of Nmbr

• These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK) [6].
• GRPR gene expression was detected predominantly in utero, whereas NMBR and BRS-3 genes were expressed from embryonic days 13-16 and on multiple postnatal days [7].
• NMB inhibited cross-linking specifically and saturably with an IC50 of 4.8 and 6.1 nM for C-6 and NMB-R transfected cells, respectively, and there was a close correlation between its ability to inhibit binding and its ability to inhibit cross-linking [8].
• The open reading frame of the putative GRP-R gene encodes for a 384-amino-acid protein which demonstrates 48% identity with the mouse BRS-3 protein and 53% identity with the mouse NMB-R protein [9].
• Therefore, in the present study we explored the ligand-receptor interactions including kinetics, stoichiometry, internalization, degradation and regulation by guanine nucleotide binding proteins with the NMB-R and compared it to the GRP-R [10].

Anatomical context of Nmbr

• The distinct regional distribution of NMB-R and GRP-R mRNA in the brain suggests that both bombesin receptor subtypes play independent roles in mediating many of the dramatic effects of bombesin-like peptides in the central nervous system [5].
• Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton [6].
• In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides [6].
• These relative affinities were almost identical to those for the NMB receptor subtype on rat oesophageal tissue and for Balb 3T3 cells stably transfected with the NMB receptor subtype [1].
• Peptide-N4-(N-acetyl-beta- glucosaminyl)asparagine amidase F (PNGase F) digestion increased the mobility of the original band in C-6, NMB-R, and GRP-R transfected cell membranes [8].

Associations of Nmbr with chemical compounds

• 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 [11].
• These results suggest that the hydroxyl group of Tyr(220) in uTM5 of NMBR plays a critical role for high selectivity of PD168368 for NMBR over GRPR [12].
• Modulation of 5-HT system in mice with a targeted disruption of neuromedin B receptor [13].
• D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists [14].
• Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists [14].

Other interactions of Nmbr

• In the reverse study using gain-of-affinity NMBR chimeras, only replacement of EC3 of NMBR markedly increased GRP affinity [15].
• Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues [16].
• Serial partial deglycosylation of cross-linked NMB-Rs with PNGase F treatment for different incubation periods revealed one band of partially glycosylated receptor (53 kDa) besides the fully glycosylated and fully deglycosylated ones, showing that NMB-R has two oligosaccharide chains [8].
• Neuraminidase digestion slightly increased the mobility of the original band in NMB-R transfected cell membranes; however, it had no effect on GRP-R transfected cell membranes [8].
• Moreover, the plasma corticosterone level under restraint stress was elevated in NMB-R-deficient mice compared to wild-type mice [13].

Analytical, diagnostic and therapeutic context of Nmbr

• To investigate the basis for this, we used a chimeric receptor approach to make both GRPR loss of affinity and NMBR gain of affinity chimeras and a site-directed mutagenesis approach [17].
• CONCLUSION: 177Lu-AMBA binds with nanomolar affinity to GRP-R and NMB-R, has low retention of radioactivity in kidney, demonstrates a very favorable risk-benefit profile, and is in phase I clinical trials [18].
• By receptor autoradiography, Lu-AMBA binds specifically to GRP-R (0.8 nmol/L) and to the neuromedin B receptor (NMB-R) (0.9 nmol/L), with no affinity for the bb3 receptor (>1,000 nmol/L) [18].
• Furthermore, a quantitative RT-PCR analysis revealed that 5-HT(1A)-receptor gene expression is downregulated in NMB-R-deficient mice at the whole brain level [19].
• While HPLC analysis showed that 5-HT content in the whole brain does not differ between NMB-R-deficient and wild-type mice, an immunohistochemical analysis of brain sections showed that 5-HT expression in the dorsal raphe (DR) nucleus is elevated in NMB-R-deficient mice [19].

References