The bombesins include structurally related pep tides that were first isolated from amphibian toad skin. Bombesin is a 14-amino acid peptide originally isolated from the skin of Bombina orientalis. The human gastrin releasing peptide (GRP) gene has been found to encode a number of bombesin-like peptides. Additional members of the bombesin family have been isolated directly from the gut, e.g., gastrin-releasing peptide and neuromedin C. Neuromedin C is a 10 amino acid peptide; its aa sequence follows immediately: (G-N-H-W-A-V G-H-L-M--NH2). This sequence results from enzymatic degradation of the 17 amino terminal end of gastrin releasing peptide.
A toad’s bombesin peptide and a human’s gastrin releasing peptide share 9 identical amino acid pep tides sequence; see Figure 1A. The bombesin peptide sequence is colored green while the GRP is colored red. The carboxy ends of both peptides are identical over the last 7 residues and are colored gold. From the entire sequence of 14 amino acids of bombesin, 9 amino acids are identical to the human GRP’s C-terminus of 14 amino acids. This suggests that there is a GRP genetic linkage between toads and man.
Fig1. A toad’s bombesin peptide and a human’s gastrin-releasing peptide (GRP) share identical amino acid peptide sequence. (A) A toad’s bombesin peptide (colored green) has 14 amino acids while the human GRP (colored red) has 27 amino acids. Both of these peptides have a C-terminal amidation terminus. When the sequence of identical amino acids in the two peptides was identified, they are colored gold. (B) Photograph of an oriental fire-bellied toad (Bombina orientalis). It is one of ~3,500 species of toads.
Bombesin was originally discovered and isolated from the skin of the oriental fire-bellied toad (Bombina orientalis); see Figure 1B. The bombesin peptide sequence has been reported to occur in gastrointestinal nerves of mammals, while in toads, frogs and birds it occurs in endocrine cells.
The bombesin present in the skin of frogs has been shown to stimulate smooth muscle contraction. Also bombesin was found to interfere with the metabolic processes of the toad’s body. This results in an increase of bodily waste products that accumulate in the frog’s glands and that could be released as a defense mechanism when the frog is threatened.
Also the potential medical-pharmaceutical significance of products derived from amphibian skin secretions have been extensively explored by pharmaceutical companies. Molecular biology studies in toads revealed that the identical mRNA is expressed in brain, skin, and stomach to the bombesin peptides. Interestingly in skin, it is processed only to bombesin (14 amino acids), whereas in the stomach it is also processed to a large form, similar in size to mammalian GRP (27 amino acids).
The presence of human gastrin releasing peptide in the stomach’s fundus and antrum and the jejunum, ileum, and colon as well as with the peripheral and central nervous systems has been determined. In all these systems, GRP functions largely as a neurotransmitter where it is a strong stimulator of other gut hormones, including gastrin, CCK, enteroglucagon, motilin, PP, PYY as well as somatostatin, insulin, and glucagon.
