BR-bombesin: a novel bombesin-related peptide from the skin secretion of the Chaco tree frog (Boana raniceps) with physiological gastric effects
2022
de Sousa, Nayara Alves | Marani, Mariela M. | Lopes, André Luís Fernandes | Silva, Emanuelle Morais | Barbosa, Eder Alves | Vasconcelos, Andreanne Gomes | Kuzniewski, Felipe T. B. | Lustosa, Suellen Sousa | Gomes, Karina Pereira | Colugnati, Diego Basile | Rocha, Jefferson A. | Santos, Lucianna Helene | Benquerer, Marcelo P. | Quelemes, Patrick | Véras, Leiz | Moreira, Daniel C. | Gadelha, Kalinne Kelly Lima | Magalhães, Pedro Jorge Caldas | Plácido, Alexandra | Eaton, Peter | Nicolau, Lucas | Medeiros, Jand Venes R. | Leite, José R. S. A.
Bombesin mediates several biological activities in the gastrointestinal (GI) tract and central nervous system in mammals, including smooth muscle contraction, secretion of GI hormones and regulation of homeostatic mechanisms. Here, we report a novel bombesin-like peptide isolated from Boana raniceps. Its amino acid sequence, GGNQWAIGHFM-NH₂, was identified and structurally confirmed by HPLC, MS/MS and 454-pyrosequencing; the peptide was named BR-bombesin. The effect of BR-bombesin on smooth muscle contraction was assessed in ileum and esophagus, and its anti-secretory activity was investigated in the stomach. BR-bombesin exerted significant contractile activity with a concentration–response curve similar to that of commercially available bombesin in ileum strips of Wistar rats. In esophageal strips, BR-bombesin acted as an agonist, as many other bombesin-related peptides act, although with different behavior compared to the muscarinic agonist carbachol. Moreover, BR-bombesin inhibited stomach secretion by approximately 50% compared to the untreated control group. This novel peptide has 80% and 70% similarity with the 10-residue C-terminal domain of human neuromedin B (NMB) and human gastrin releasing peptide (GRP10), respectively. Molecular docking analysis revealed that the GRP receptor had a binding energy equal to − 7.3 kcal.mol⁻¹ and − 8.5 kcal.mol⁻¹ when interacting with bombesin and BR-bombesin, respectively. Taken together, our data open an avenue to investigate BR-bombesin in disorders that involve gastrointestinal tract motility and acid gastric secretion.
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