Chemical Identity

Property	Value
Name	Bombesin
Source	Bombina bombina, Bombina variegata (European fire-bellied toad) skin
Sequence	pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH₂
Abbreviation	pEQRLGNQWAVGHLM-NH₂
Length	14 amino acids
Chemical Formula	C₇₁H₁₁₀N₂₀O₂₁S
Molecular Weight	1622.9 Da
CAS Number	31396-25-7
PDB Structures	1JRJ (NMR), 1GQB (NMR)

Discovery

Bombesin was first isolated from the skin of Bombina bombina (European fire-bellied toad) by Anastasi, Erspamer, and Bucci in 1971. It was one of the first bioactive peptides discovered in amphibian skin.

The name “bombesin” derives from the genus name Bombina.

Mammalian Homologs

Bombesin has two mammalian homologs:

Peptide	Source	Receptor	Sequence Homology
Bombesin	Frog skin	BB1 (NMBR)	—
Neuromedin B (NMB)	Mammalian brain	BB1 (NMBR)	60% C-terminal
Gastrin-releasing peptide (GRP)	Mammalian GI tract	BB2 (GRPR)	40% C-terminal

Receptors

Bombesin Receptor Family

Receptor	Gene	Distribution	Function
BB1 (NMBR)	TACR3	Brain, GI tract	Feeding, thermoregulation
BB2 (GRPR)	GRPR	Brain, GI tract, lung	Growth, feeding, anxiety
BRS3	BRS3	Brain, lung	Glucose metabolism

Signaling

Bombesin binds BB1/BB2 → Gαq → PLCβ → IP₃ + DAG → Ca²⁺ + PKC → MAPK, PI3K/AKT, STAT3 pathways

Physiological Effects

Growth Stimulation

• Cell proliferation: Bombesin/GRP is a potent mitogen for many cell types
• Mechanism: Activates MAPK/ERK, PI3K/AKT, and STAT3 signaling
• Cancer relevance: GRP is produced by small cell lung cancer (SCLC) in an autocrine fashion

Feeding Behavior

• Central injection: Potent feeding stimulation in rats and mice
• Mechanism: Acts on BB2 receptors in the hypothalamus
• Clinical relevance: Bombesin analogs under investigation for appetite disorders

Thermoregulation

• Central injection: Hypothermia in mammals
• Mechanism: BB1 receptor activation in the preoptic area

GI Function

• Gastric acid secretion: Stimulates gastrin release
• Pancreatic enzyme secretion: Stimulates pancreatic exocrine function
• Gallbladder contraction: Contracts smooth muscle

Cancer Biology

Small Cell Lung Cancer (SCLC)

• Autocrine growth loop: SCLC cells produce both GRP and GRPR
• Diagnostic marker: Elevated GRP levels in SCLC patients
• Therapeutic target: GRPR antagonists in clinical trials

Prostate Cancer

• Overexpression: GRPR is overexpressed in prostate cancer
• Imaging: ⁶⁸Ga-GRPR-PSMA PET imaging
• Therapy: GRPR-targeted radioligand therapy

Other Cancers

• Breast cancer (GRPR overexpression)
• Colorectal cancer (GRP autocrine loop)
• Gastrinoma (GRP-like peptides)

Drug Development

GRPR Antagonists

Drug	Type	Status	Indication
RC-3095	Peptide antagonist	Preclinical	Cancer
PD176252	Non-peptide antagonist	Research	Cancer
⁶⁸Ga-NeoB	PET tracer	Clinical imaging	Prostate cancer
¹⁷⁷Lu-NeoB	Radioligand therapy	Phase I/II	Prostate cancer

Diagnostic Applications

• ⁶⁸Ga-NeoB PET: GRPR-positive prostate cancer imaging
• ⁹⁹ᵐTc-NeoB SPECT: Sentinel lymph node detection
• ¹¹¹In-NeoB: Neuroendocrine tumor imaging

Research Applications

• Growth factor signaling: Model for studying autocrine growth loops
• Neuroscience: Studying feeding behavior, thermoregulation, anxiety
• Cancer biology: GRP as oncogene, GRPR as therapeutic target
• Drug development: GRPR imaging agents and radioligands

References

1. Anastasi A, Erspamer V, Bucci M. “Isolation and structure of bombesin and alytesin.” Experientia 27:166-167, 1971. doi:10.1016/0014-5793(71)80308-4
2. Spindel ER, et al. “Cloning and characterization of a cDNA encoding the bombesin/gastrin-releasing peptide receptor.” Science 249:806-810, 1990. doi:10.1126/science.249.4969.806
3. Moody TW, et al. “Neuropeptides and their receptors in small cell lung cancer.” Lung Cancer 24:77-92, 1999. doi:10.1016/S0169-5009(99)00006-0
4. Reubi JC, et al. “Bombesin receptors in human breast cancer.” Journal of Clinical Endocrinology and Metabolism 73:252-256, 1991.
5. Berridge MJ. “Inositol trisphosphate, calcium, and cell signaling.” Advances in Second Messenger and Phosphoprotein Research 26:193-206, 1992.