Bombesin

Discovery and Origin

Bombesin was first isolated in 1970 from the skin of the European fire-bellied toad, Bombina bombina, by Viktor Erspamer and colleagues. The peptide was named after the genus Bombina and rapidly attracted interest due to its potent effects on gastrointestinal secretion. Although originally identified in amphibian tissue, bombesin-like peptides are widely distributed throughout the mammalian nervous system and gastrointestinal tract, where they function as neurotransmitters and paracrine regulators.

Amino Acid Sequence and Structure

The 14-amino acid sequence of bombesin is: pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2. The C-terminal amidation is essential for full biological activity. The peptide adopts an alpha-helical conformation in hydrophobic environments, particularly in the C-terminal region spanning residues 6-14, which constitutes the pharmacophore for receptor binding. NMR studies in solution reveal a bent structure with a hydrophobic core formed by Trp8, Val10, and Leu13.

Receptor Pharmacology

Bombesin exerts its effects primarily through the BB2 receptor (neuromedin B receptor), a Gq-coupled G protein-coupled receptor. A related receptor, BB1 (gastrin-releasing peptide receptor), also mediates bombesin actions. BB2 activation triggers phospholipase C stimulation, leading to inositol trisphosphate production and intracellular calcium mobilization. The receptor exhibits high affinity for bombesin (Kd approximately 1 nM) and is expressed in brain, gastrointestinal tract, and reproductive tissues.

Physiological Functions

Bombesin is a potent stimulator of gastrin release from gastric G cells, thereby promoting gastric acid secretion. In the central nervous system, bombesin-like peptides regulate thermoregulation, satiety, and anxiety-related behaviors. Intracerebroventricular administration of bombesin produces hypothermia and reduces food intake in rodents. Peripheral effects include stimulation of pancreatic enzyme secretion, gallbladder contraction, and smooth muscle contraction in the gastrointestinal tract.

Clinical and Research Applications

Bombesin analogs conjugated to radionuclides have been explored as diagnostic imaging agents for prostate cancer and small-cell lung carcinoma, which frequently overexpress BB2 receptors. The ability to deliver targeted radioligands to receptor-positive tumors using bombesin derivatives represents a promising theranostic approach. Additionally, bombesin antagonists are under investigation for the management of obesity and appetite disorders.

References

Erspamer V, Melchiorri P, Broccardo M, et al. A bombesin-like octapeptide in anuran amphibian skin. Peptides. 1985;6:373-380.
Jensen RT, Battey JF, Spindel ER, Benya RV. International Union of Pharmacology. LXVI. The bombesin receptor family. Pharmacological Reviews. 2008;60:1-42.
Schroeder RP, Muller C, Bruneman TC, et al. Bombesin receptor antagonists in oncology. Current Opinion in Pharmacology. 2014;14:72-79.