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Bombesin Family Related Drug Discovery Products

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Bombesin (Bn), a tetradecapeptide with a COOH terminus concluding in Gly-His-Leu-Met-NH2, was discovered to closely resemble two mammalian Bn-related peptides, gastroin-releasing peptide (GRP) and neuromedin B. (NMB). Seven COOH terminal amino acids are shared by Bn and the 27-amino-acid peptide GRP, which was originally isolated from swine stomach, explaining why they have similar biological roles. NMB is a decapeptide that was isolated from pig spinal cord and is similar to the frog peptide ranatensin. Its COOH terminus is composed of the amino acids Gly-His-Phe-Met-NH2. These peptides are widely distributed throughout the peripheral tissues and central neurological systems of mammals, especially in the gastrointestinal (GI) tract.

The evolutionary lineage of the bombesin.Fig.1 The evolutionary lineage of the bombesin.1,2

To meet the needs of drug discovery, Creative Biolabs can provide a wide variety of bombesin family related assays and products:

Overview of Bombesin Receptor

NMB and BB1 receptor activation are known to potently inhibit thyrotropin release from the pituitary, acting as an autocrine and paracrine regulator. They also have significant effects on the central nervous system, including those on satiety, thermoregulation, mediating stress and fear responses, and other behaviors like spontaneous activity. It was suggested that antagonists to the BB1-receptor as well as the BB2-receptor would represent an unique class of anxiolytic drugs given the evidence that BB1-receptor activation impacts both anxiety and fear responses, whereas the BB2-receptor influences the fear response.

A wide range of pharmacological and biological responses are known to be triggered by GRP and the stimulation of BB2-receptors. These include potent effects on immune cells, stimulation of secretion and hormone release, potent growth effects on normal and neoplastic tissues, and potent CNS effects including regulating circadian rhythm, thermoregulation, anxiety, satiety, and various behavioral features.

The synthetic agonist [D-Tyr6, -Ala11, Phe13, Nle14] bombesin 6-14 is a nonselective agonist for this receptor and the natural ligand is unknown because there are no known antagonists for this receptor. In fetal and developing lungs, BB3-receptor-containing cells are expressed, and their expression rises in response to injury, according to recent studies. A recent receptor localization research revealed that the BB3-receptor was present in the highest densities in the myenteric/submucosal ganglia and the C-kit interstitial cells of Cajal, providing more evidence for its potential function in the GI tract.

Bombesin Receptor Drug Discovery

  • Gliomas

GRPR was found in all 34 cases of human gliomas in an immunocytochemical investigation. In all patients' tumoral tissue and tumor-associated endothelial cells, GRPRs were found, while in normal brain tissue, they were only found in the neurons and not in the glial cells.

  • Neuroblastomas

Numerous investigations have shown that neuroblastoma tumor tissue and neuroblastoma cell lines contain Bn-related peptides and BnRs. According to immunocytochemical analyses of 33 human neuroblastomas, 73% of them exhibited GRPR, which is more expressed in undifferentiated tumors than benign tumors.

  • Medulloblastomas

PCR and immunohistochemistry were used to check the expression of GRPR in three different medulloblastoma cell lines (DAOY, D283, ONS76). All three medulloblastoma cell lines had GRPR and GRPR mRNA, according to PCR and immunohistochemistry analyses.

References

  1. Hirooka, Asuka, et al. "The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus." Scientific reports 11.1 (2021): 13315.
  2. Image retrieved from Figure 7 " The evolutionary lineage of the gastrin-releasing peptide (GRP)/bombesin. " Hirooka, et al. 2021, used under CC BY 4.0. The original image was modified by extracting and the title was changed to " The evolutionary lineage of the bombesin.".

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