The Discovery of Bombesin
| Category | Research |
|---|---|
| Also known as | bombesin history, Erspamer bombesin, GRP |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | historybombesingrpamphibian-peptidesgut-brain-peptides |
Overview
Bombesin is a 14-amino-acid peptide originally isolated in 1971 by Vittorio Erspamer and colleagues at the University of Rome from the skin of the European fire-bellied toad (Bombina bombina). The peptide has potent effects on gastric acid secretion, smooth muscle contraction, and thermoregulation. Erspamer's group spent decades systematically characterizing amphibian skin peptides, yielding a large catalog of bioactive molecules including bombesin, dermorphin, and various tachykinins and bradykinins.
Bombesin's biological activity in mammals hinted at a homologous mammalian peptide, which was identified in 1978 by Timothy McDonald, Hans-Jörg Jörnvall, and Viktor Mutt at the Karolinska Institute. They named it gastrin-releasing peptide (GRP) for its ability to stimulate gastrin release. GRP and the related peptide neuromedin B form the mammalian "bombesin-like peptide" family.
Bombesin and its mammalian relatives act through three G protein-coupled receptors: BB1 (neuromedin B receptor), BB2 (GRP receptor), and BB3 (bombesin receptor subtype 3, orphan for many years). These receptors are expressed widely in the central nervous system, gastrointestinal tract, pancreas, and in many cancers.
Key People
- Vittorio Erspamer (1909–1999): Italian pharmacologist who catalogued an enormous number of bioactive amphibian peptides.
- Pietro Melchiorri: Long-time Erspamer collaborator.
- Timothy McDonald and Viktor Mutt: Identified mammalian GRP.
- Robert T. Jensen: American gastroenterologist who led extensive clinical and receptor pharmacology studies.
Timeline
- 1971: Erspamer and colleagues isolate bombesin from Bombina bombina skin.
- 1978: GRP is identified as the mammalian bombesin homolog.
- 1980: Neuromedin B is isolated.
- 1990s: BB1, BB2, and BB3 receptors are cloned.
- 2000s: Bombesin receptor-targeted imaging and therapeutic agents are developed for prostate and breast cancer.
- 2010s–2020s: Continued exploration of BB3 in metabolic disease.
Background
Amphibian skin has long been known as a rich source of bioactive peptides, evolved primarily for defense against microbes and predators. Erspamer's systematic sampling across many species of frogs and toads produced an unusually productive natural-product discovery program. Many of the peptides he isolated were homologs or analogs of mammalian hormones, neuropeptides, or antimicrobial peptides, making amphibian skin an important window into vertebrate peptide evolution.
In mammals, GRP and neuromedin B participate in the regulation of gastric acid secretion, smooth muscle contraction, pancreatic enzyme release, and satiety. Central GRP signaling has been implicated in fear memory, itch transmission, and stress responses. The diverse tissue distribution of bombesin-like peptide receptors makes the family a target for both oncology and neurology research.
Modern Relevance
Bombesin receptor-targeted imaging has become an active area of nuclear medicine. Many prostate cancers overexpress the GRP receptor, and radiolabeled bombesin analogs (for example, tagged with 68-gallium or 177-lutetium) are studied for PET imaging and peptide receptor radionuclide therapy. Similar approaches are pursued in breast, small-cell lung, and certain brain cancers.
Beyond oncology, BB3 has attracted interest as a potential target for obesity and diabetes, because BB3 knockout mice develop obesity and metabolic abnormalities. Small-molecule BB3 agonists have advanced to early-stage clinical evaluation. For related amphibian-derived peptides, see substance-p-history.
Related Compounds
Related entries
- The Discovery of Cholecystokinin— Cholecystokinin, the gut peptide that triggers gallbladder contraction and pancreatic enzyme release, was identified by Ivy and Oldberg in 1928.
- The Discovery of Gastrin— Gastrin, the stomach hormone that drives gastric acid secretion, was proposed by Edkins in 1905 and purified by Gregory and Tracy in the 1960s.
- History of Substance P— Substance P, the prototypical tachykinin, was first described in 1931 by von Euler and Gaddum and sequenced in 1971 by Chang and Leeman.