Bombesin is a naturally occurring peptide with diverse physiological effects. This neurohormone polypeptide, composed of 14 amino acids, was first identified in amphibians. Its discovery led to understanding a broader family of related peptides impacting various bodily systems. Bombesin and its mammalian counterparts continue to be subjects of extensive study, particularly concerning their roles in health and disease.
Origins and Related Peptides
Bombesin was initially isolated from the skin of the European fire-bellied toad, Bombina bombina. It served as the prototype for a family of similar compounds. Scientists later discovered two comparable peptides in mammals: Gastrin-Releasing Peptide (GRP) and Neuromedin B (NMB). These mammalian peptides share structural similarities with amphibian bombesin and are considered its evolutionary relatives.
GRP is a 27-amino acid peptide, first identified in the porcine stomach, and is considered the mammalian equivalent of bombesin due to its similar biological and immunological properties. Neuromedin B is another bombesin-like peptide found in mammals, initially identified in the porcine spinal cord. Both GRP and NMB exert their effects by binding to specific receptors, which are related to those for amphibian bombesin. Amphibian bombesin is not directly found in humans; GRP and NMB are the peptides relevant to human biology and are often referred to collectively as “bombesin-like peptides” when discussing human physiology.
Physiological Actions
Gastrin-Releasing Peptide (GRP) and Neuromedin B (NMB) play varied roles in maintaining normal bodily functions. In the gastrointestinal system, GRP is a significant regulator of digestive processes. It stimulates the release of gastrin, a hormone promoting gastric acid secretion, aids in gut motility, and influences the growth of gastrointestinal tissues. This action helps in the efficient breakdown and absorption of food.
Beyond digestion, these peptides also influence the central nervous system. GRP and NMB are involved in regulating appetite, acting as a signal to stop eating behavior, similar to cholecystokinin. They also play roles in thermoregulation, helping the body maintain a stable internal temperature, and are implicated in stress responses. The influence of bombesin-like peptides extends to the endocrine system, where they can modulate the release of certain hormones, contributing to overall physiological balance.
These physiological actions are mediated through specific receptors found on cell surfaces. There are three main types of bombesin receptors in mammals: BB1 (Neuromedin-B receptor or NMBR), BB2 (Gastrin-Releasing Peptide Receptor or GRPR), and BB3 (Bombesin Receptor Subtype-3 or BRS-3). GRP primarily binds to the GRPR (BB2), while NMB has a higher affinity for the NMBR (BB1). These receptors are G-protein-coupled receptors, meaning they initiate a cascade of internal cellular events upon binding with their respective peptides, leading to the observed biological effects.
Connection to Disease
Dysregulation of bombesin-like peptides and their receptors has been linked to various disease states, with a notable association in several types of cancer. These peptides can act as growth factors, promoting tumor cell proliferation and survival. One of the most well-established connections is with small cell lung cancer (SCLC), where Gastrin-Releasing Peptide (GRP) and its receptor (GRPR) are often overexpressed. This overexpression can create an autocrine loop, meaning the cancer cells produce GRP, which then stimulates their own growth through GRPR, contributing to tumor progression.
The involvement of bombesin-like peptides extends to other malignancies as well. In prostate cancer, GRP and its receptor are frequently found at elevated levels, suggesting a role in tumor development and spread. Similarly, gastrointestinal cancers, including those of the pancreas and colon, show dysregulation of these peptides and their receptors, indicating their contribution to cancerous growth in these areas. Targeting the bombesin receptor system has therefore become an area of interest for potential therapeutic interventions in these cancers.
Beyond cancer, bombesin-like peptides have also been implicated in other conditions, such as inflammation and obesity. The broad involvement of these peptides highlights their complex physiological roles and the potential consequences when their normal regulation is disrupted. Understanding these connections provides insights into disease mechanisms and pathways for future research.