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Gene Review

NMBR  -  neuromedin B receptor

Homo sapiens

Synonyms: BB1, Epididymis tissue protein Li 185a, NMB-R, Neuromedin-B receptor, Neuromedin-B-preferring bombesin receptor
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Disease relevance of NMBR

  • Additionally, we have detected transcripts for GRPR and NMBR in four of seven and seven of seven cases, respectively, of cultured non-small cell lung carcinomas (NSCLC) [1].
  • Our study indicates that GRPR and NMBR are widely distributed in human ovarian carcinomas with BRS-3 being found in Stage IV tumors [2].
  • Both GRP-R and NMB-R mRNA expression was detected at varying levels in a panel of human lung cancer cell lines [3].
  • The mechanism is not known, and a potent and specific GRP-R antagonist BIM26226, which has low affinity for NMB-R, was used in vivo in athymic nude mice bearing gastrinoma subcutaneously [4].

High impact information on NMBR


Biological context of NMBR

  • Results of 125I-[D-Tyr0]NMB displacement assays using unlabeled NMB for competition indicated that high affinity NMB binding was determined by amino acid sequences in transmembrane domain V (TM-V) of the NMB-R [9].
  • As a first step, we examined the distribution of expression of GRP-R and NMB-R mRNA during rat embryonic development to identify changing spatio-temporal patterns of gene expression [10].
  • Comparison of the mouse and human receptor sequences indicates 90% (NMB-R) and 85% (BRS-3) sequence homology at the amino-acid level [11].

Anatomical context of NMBR

  • Using the reverse transcription-polymerase chain reaction (RT-PCR), we have detected mRNA for the neuromedin B receptor (NMBR) in all 14 of the NSCLC cell lines examined [12].
  • All actions of bombesin were blocked by BME (D-Phe(6)-bombesin-(6-13)-methylester), a selective GRP receptor antagonist, but not by the NMB receptor antagonist BIM-23127 (D-Nal-cyclo[Cys-Tyr-D-Trp-Orn-Val-Cys]-Nal-NH(2)).We conclude that HPAF cells express mRNA for GRP receptors and that functional receptors are present in the cell membrane [13].
  • Only NMB-R-null mice accumulated fewer lung mast cells after bombesin treatment [14].
  • After expression in Xenopus oocytes, a GRP-R-specific antagonist was effective in blocking responses elicited from the cloned GRP-R, but not the NMB-R [3].
  • In contrast, the distribution of expression of NMB-R mRNA is more limited (upper gastrointestinal tract, bladder, and central nervous system) and is observed at later embryonic stages [10].

Associations of NMBR with chemical compounds


Other interactions of NMBR

  • We have also amplified message for NMBR in five of five fresh bronchial biopsies, but message for GRPR could not be detected [1].
  • An amplified fragment was detected for GRPR in seven of nine cases, for NMBR in six of 10 cases, and the BRS-3 in three of nine cases [1].
  • The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors [17].
  • In conclusion, BIM- 23127 is the first hUT receptor antagonist identified to date and should not be considered as a selective neuromedin B receptor antagonist [17].

Analytical, diagnostic and therapeutic context of NMBR

  • Recent analysis using NMB-R-deficient mice, generated by gene-targeting technique, enables to distinguish functional properties of NMB-R from GRP-R [5].
  • PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor [18].
  • 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 [19].
  • 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) [19].
  • By immunohistochemistry, both NMB and NMB-R were expressed in normal and cancerous colonic epithelial tissues [20].


  1. Expression of mRNA for three bombesin receptor subtypes in human bronchial epithelial cells. DeMichele, M.A., Davis, A.L., Hunt, J.D., Landreneau, R.J., Siegfried, J.M. Am. J. Respir. Cell Mol. Biol. (1994) [Pubmed]
  2. The presence of receptors for bombesin/GRP and mRNA for three receptor subtypes in human ovarian epithelial cancers. Sun, B., Schally, A.V., Halmos, G. Regul. Pept. (2000) [Pubmed]
  3. Two distinct bombesin receptor subtypes are expressed and functional in human lung carcinoma cells. Corjay, M.H., Dobrzanski, D.J., Way, J.M., Viallet, J., Shapira, H., Worland, P., Sausville, E.A., Battey, J.F. J. Biol. Chem. (1991) [Pubmed]
  4. Mechanisms of bombesin on growth of gastrinoma (PT) in vivo. Chu, K.U., Ishizuka, J., Battey, J.F., Uchida, T., Beauchamp, R.D., Townsend, C.M., Thompson, J.C. Dig. Dis. Sci. (1996) [Pubmed]
  5. Neuromedin B. Ohki-Hamazaki, H. Prog. Neurobiol. (2000) [Pubmed]
  6. Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells. Frankel, A., Tsao, M.S., Viallet, J. Cancer Res. (1994) [Pubmed]
  7. Genome-wide linkage to chromosome 6 for waist circumference in the Framingham Heart Study. Fox, C.S., Heard-Costa, N.L., Wilson, P.W., Levy, D., D'Agostino, R.B., Atwood, L.D. Diabetes (2004) [Pubmed]
  8. Four amino acid residues are critical for high affinity binding of neuromedin B to the neuromedin B receptor. Sainz, E., Akeson, M., Mantey, S.A., Jensen, R.T., Battey, J.F. J. Biol. Chem. (1998) [Pubmed]
  9. The fifth transmembrane segment of the neuromedin B receptor is critical for high affinity neuromedin B binding. Fathi, Z., Benya, R.V., Shapira, H., Jensen, R.T., Battey, J.F. J. Biol. Chem. (1993) [Pubmed]
  10. Bombesin receptor gene expression during mammalian development. Battey, J., Wada, E., Wray, S. Ann. N. Y. Acad. Sci. (1994) [Pubmed]
  11. Cloning and expression of the neuromedin B receptor and the third subtype of bombesin receptor genes in the mouse. Ohki-Hamazaki, H., Wada, E., Matsui, K., Wada, K. Brain Res. (1997) [Pubmed]
  12. Evidence for autocrine actions of neuromedin B and gastrin-releasing peptide in non-small cell lung cancer. Siegfried, J.M., Krishnamachary, N., Gaither Davis, A., Gubish, C., Hunt, J.D., Shriver, S.P. Pulmonary pharmacology & therapeutics. (1999) [Pubmed]
  13. GRP-receptor-mediated signal transduction, gene expression and DNA synthesis in the human pancreatic adenocarcinoma cell line HPAF. Burghardt, B., Wenger, C., Barabás, K., Rácz, G., Oláh, A., Flautner, L., Coy, D.H., Gress, T.M., Varga, G. Peptides (2001) [Pubmed]
  14. Bombesin-like peptides and mast cell responses: relevance to bronchopulmonary dysplasia? Subramaniam, M., Sugiyama, K., Coy, D.H., Kong, Y., Miller, Y.E., Weller, P.F., Wada, K., Wada, E., Sunday, M.E. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  15. Bombesin-like peptide receptor subtypes promote mitogenesis, which requires persistent receptor signaling. Feldman, R.I., Bartholdi, M.F., Wu, J.M. Mol. Pharmacol. (1996) [Pubmed]
  16. Pharmacological profiles of two bombesin analogues in cells transfected with human neuromedin B receptors. Ryan, R.R., Taylor, J.E., Daniel, J.L., Cowan, A. Eur. J. Pharmacol. (1996) [Pubmed]
  17. The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors. Herold, C.L., Behm, D.J., Buckley, P.T., Foley, J.J., Wixted, W.E., Sarau, H.M., Douglas, S.A. Br. J. Pharmacol. (2003) [Pubmed]
  18. Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368. Ryan, R.R., Katsuno, T., Mantey, S.A., Pradhan, T.K., Weber, H.C., Coy, D.H., Battey, J.F., Jensen, R.T. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  19. 177Lu-AMBA: Synthesis and characterization of a selective 177Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. Lantry, L.E., Cappelletti, E., Maddalena, M.E., Fox, J.S., Feng, W., Chen, J., Thomas, R., Eaton, S.M., Bogdan, N.J., Arunachalam, T., Reubi, J.C., Raju, N., Metcalfe, E.C., Lattuada, L., Linder, K.E., Swenson, R.E., Tweedle, M.F., Nunn, A.D. J. Nucl. Med. (2006) [Pubmed]
  20. Neuromedin B and its receptor are mitogens in both normal and malignant epithelial cells lining the colon. Matusiak, D., Glover, S., Nathaniel, R., Matkowskyj, K., Yang, J., Benya, R.V. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
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