Bombesin receptor 1 (BB₁) is a member of a family of receptors that binds the 14 amino acid peptide bombesin. Bombesin was initially isolated from frog skin and it was later established that mammals express endogenous bombesin-like peptides such as gastrin-releasing peptide (GRP) and neuromedin B (NMB), 27 and 10 amino acid homologues, respectively.¹

BB₁ is the preferred receptor for NMB (therefore it is also known as NMB receptor) while BB₂ is the preferred receptor for GRP.² BB₃ was the third member of the bombesin family of receptors to be cloned based upon its sequence similarity to BB₁ and BB₂.¹ The affinity of BB₃ for bombesin is lower than that of the BB₁ and BB₂ receptors, as are its affinities for NMB and GRP. This suggests that the endogenous mammalian ligand for the BB₃ receptor remains to be identified.

All three bombesin receptors are members of the 7-transmembrane domain, G protein-coupled receptor (GPCR) superfamily. BB₁ is coupled to a G_q/11 protein that activates phospholipase C (PLC) and leads to production of inositol 1,4,5-trisphosphate (InsP₃), intracellular Ca²⁺ mobilization, and cell growth.¹

BB₁ is expressed in the brain where it likely mediates the inhibition of food intake and regulates the stress and fear response. BB₁ and its ligand NMB are expressed in the pituitary where they participate in the regulation of thyroid-stimulating hormone (TSH) secretion in both autocrine and paracrine fashions.³ In the periphery, BB₁ is expressed in the gastrointestinal and urogenital smooth muscle but its physiological function in these tissues is unclear.

Finally, BB₁ is over-expressed in several human tumors especially colon and non-small lung cancer where it acts as a growth factor receptor inducing tumor growth. BB₁ is considered a potential target for the development of both diagnostics and anti-cancer therapies.⁴