In the brain, bombesin is known as neuromedin B and is involved in smooth muscle contraction.[21] Bombesin is present in regions of the trachea, bronchus, and within the whole lung at different stages of human fetal development. Bombesin is present in neonates, children, and adults.[22] 

Bombesin causes the release of endogenous gastrin, activating sensory neurons located in the gastric fundus responsible for gastric smooth muscle motility and luminal protection. Activation of sensory neurons causes increased production of nitric oxide through activation of constitutive nitric oxide synthase. Activation of nitric oxide synthase leads to an increase in gastric mucosal blood flow and makes the stomach less susceptible to injury from luminal irritants.[23] Bombesin is the most effective promotor of G cell-regulated gastrin release plus subsequent stimulate gastric acid excretion.[16][24][25][24]

Bombesin is predominantly known to regulate homeostasis within the gastrointestinal tract.[1] When binding to gastrointestinal luminal receptors, bombesin produces adverse effects such as nausea, vomiting, and diarrhea. Bombesin is the major source of negative feedback signals that stop eating behavior second only to cholecystokinin.[26] 

Bombesin can function as a growth factor through autocrine or paracrine mechanisms, which may modulate the growth of various benign and neoplastic tissues. Therefore, the problem this protein can address is that of prostate precision. The fact that radiolabeling cannot differentiate between benign hyperplastic prostate cells and malignant carcinoma cells limits their diagnostic value. Hence, there has been much effort put into developing new prostate carcinoma–specific PET tracers with high diagnostic sensitivity and specificity.[27][28]

Bombesin binds to the G-protein receptor. G protein-coupled reaction occurs, which activates a phosphorylation cascade. Phosphorylation cascade cleaves PIP2. PIP2 separates into inosine-monophosphate (IP3) and diacylglycerol (DAG). IP3 and DAG both increase in concentration within the cell. DAG interacts with protein kinase C (PKC). DAG-PKC interaction activates protein kinase C (aPKC). aPKC phosphorylates serine residues on intracellular target proteins.[29] Intracellular target proteins release calcium stores intracellularly.  Intracellular calcium levels increase, causing cellular depolarization. Intracellular calcium binds to synapsin, altering its conformation. Altered synapsin causes intracellular vesicle diffusion. Altered synapsin exposes calcium-binding sites on microtubules attached to intracellular vesicles. Calcium activates dynein arms causing efferent microtubules diffusion. Vesicles fuse with the plasma membrane and release their contents into the extracellular environment.[29]

Researchers believe that neuropeptides influence feeding, satiety, energy homeostasis, and other parameters associated with weight control.[30] Those involved are bombesin, insulin, and orexins. These peptides exhibit diverse effects upon the hypothalamus by acting as ligands for G protein-coupled receptors within the brain. Some tumors can produce agents such as bombesin and adrenocorticotropic hormone, which can affect caloric processing.[31][32][33] The abnormal intake and utilization of calories contribute to the altered metabolism associated with cachexic states precipitated by tumorigenesis, which leads to a cyclical chain of events which protein catabolism, glucose intolerance, and lipolysis that cannot be augmented by the addition of calories.

Inhalational exposures can precipitate an inflammatory reaction within the airways and alveoli, leading to activated neutrophils, and other inflammatory cells release proteases as part of the inflammatory process. Neutrophil-induced oxidative damage stimulates the release of profibrotic neuropeptide bombesin in the normal process of tissue repair. This mechanism appears to contribute to the pulmonary neuroendocrine cells' promotion of bombesin-like peptide immunoreactivity.[34]

Studies have correlated bombesin-like immunoreactivity with the abnormal inflammatory response seen in bronchopulmonary dysplasia.[35][36] Researchers in a study of 132 infants at 28-weeks gestation or less found that bombesin-like peptide levels elevate in the urine prior to the development of bronchopulmonary dysplasia.[37] Infants who had elevated levels of the bombesin-like peptide in their urine 1 to 4 days after birth were ten times more likely to develop bronchopulmonary dysplasia.[37] Therefore, urine bombesin-like peptide screening might allow for early therapeutic interventions to minimize disease progression.

Eosinophilic granuloma is a fibrotic lung disease almost always seen in adult cigarette smokers. One study showed that the number of pulmonary neuroendocrine cells with bombesin-like immunoreactivity increases in patients with eosinophilic granuloma.[20] Therefore neuroendocrine cell hyperplasia may lead to bombesin-like peptide elevation and subsequent monocyte and fibroblast recruitment, which contribute to granuloma formation; this would be in line with other studies which have shown bombesin to be chemotactic for monocytes and mitogenic for fibroblasts.[20]

Inhibition of Ca ++ influx inhibits the release of neurotransmitters like bombesin, acetylcholine, norepinephrine, serotonin, somatostatin, and substance P. These neurotransmitters mediate pain perception in the spinal cord. Inhibition of release into the synaptic cleft leads to decreased postsynaptic neuronal firing and transmission of nociception.[38]

Tumors of neuronal origin such as medulloblastoma, primitive neuroectodermal tumors, neuroblastoma, pineoblastoma are bombesin positive. Recently it has been suggested that bombesin-related peptides are involved in the autocrine stimulation of human small-cell lung carcinomas The growth and metastatic potential of neuroendocrine tumors. The molecular mechanisms and signaling pathways that are responsible for bombesin-like peptide-induced cell migration and invasion remain unclear.[23][39]

Bombesin exerts a stimulatory effect on the growth of human prostatic cancer cells in vitro.[34] Bombesin also has a role in prostatic epithelium growth; this would support other studies stating that prostatic carcinoma may have an endocrine, autocrine, or paracrine proliferation stimulus within the gland microenvironment.[40][41][42] This important fact provides an objective basis for the development of neuropeptides as therapeutic targets and may be helpful in the treatment of advanced prostatic carcinoma.[43][41]

Loss of bombesin receptors correlates with age-dependent obesity, hypertension, glucose intolerance, and high insulin levels. This expanded adipose deposition may, in part, be due to a decline in energy consumption without a shift in eating or movement, which infers that bombesin receptors may signify a plausible target upon which notable advancement can take place in the realm of anti-obesity agents.

Bombesin has the theoretical capability to address prostate cancer screening. Current screening methods include prostate-specific antigen serum testing, followed by a digital rectal examination. Those screening techniques do not yield information on the primary location of the carcinoma cells. Therefore, possible metastases cannot be determined or diagnosed with high accuracy. The fact that radiolabeling cannot differentiate between benign hyperplastic prostate cells and malignant carcinoma cells limits their diagnostic value. BBR and gastrin-releasing peptide receptors are over-expressed in solid malignancies and particularly in prostate cancer.[44] These receptors are over-expressed rarely and, if expressed, then only in low density in benign prostatic hyperplasia and normal prostate tissue.[45] Studies have shown that prostate tissue has a high density of receptors belonging to the bombesin receptor family.[46] This finding has sparked an interest in developing new prostate carcinoma–specific PET tracers, which would provide high diagnostic sensitivity and specificity.

Precision medicine is also known as theranostics, is a medical model that separates people into different groups with medical care tailored to the individual patient based on their predicted response or risk of disease.[47] Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumors, including prostate and breast.[48] Bombesin receptors often demonstrate significant expression on a variety of tumors. Therefore, bombesin can chaperone cytotoxic drugs straight to these tumors. A cytotoxic analog of bombesin containing doxorubicin displayed disease stabilization through phase-I clinical trials against ovarian and endometrial carcinomas.[49] It is now undergoing phase-I or phase-II clinical trials in other various malignancies.[4] 

Measuring bombesin stimulated gastrin response can serve as a marker for patients who are at very high risk for gastric cancer. Patients with late-onset hypogammaglobulinemia are at very high risk for gastric cancer. Late-onset hypogammaglobulinemia patients have reduced secretion of gastrin after stimulation with bombesin. Stimulated gastrin response can, therefore, be useful as a marker for this type of immunodeficiency. Plasma gastrin responses to stimulation with bombesin correlates with late-onset hypogammaglobulinemia. (72% sensitivity , 100% specificity). Bombesin can help to distinguish late-onset hypogammaglobulinemia from X-linked agammaglobulinemia, early-onset hypogammaglobulinemia, and lymphoproliferative cancer.[50] This differentiation would also help to identify patients with an increased risk for gastric cancer. Plasma gastrin responses to stimulation with bombesin correlates with late-onset hypogammaglobulinemia. 

A bombesin/gastrin-releasing peptide antagonist might hold promise as a possible new agent for the treatment of breast cancer.[51]