The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus

Abstract

Bombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phylogenetic viewpoint using a newly established genetic database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the ‘gut-brain peptide’ systems.

Two novel bombesin-like neuropeptides from the skin secretion of Pelophylax kl. esculentus: Ex vivo pharmacological characterization on rat smooth muscle types

“…Daum et al revealed that the skin secretion from the hybrid frog species, Pelophyla x kl. esculentus , could manifest a more potent fungicidal effect against Batrachochytrium dendrobatidis , along with a greater antimicrobial peptide diversity ( Hirooka et al, 2021 ). However, the hybrid amphibian systems are largely unstudied.…”

“…Gastrin-releasing peptides (GRP) and neuromedin-B (NMB) are two BLPs found in mammals ( Jensen et al, 2008 ). Originally isolated from porcine stomach, GRP stimulates gastrin release, smooth muscle contraction, and proliferation of epithelial cells ( Hirooka et al, 2021 ). NMB was latterly identified from porcine tissue and has been found to contract smooth muscles, influence endocrine secretion, and regulate blood pressure ( Hiroko, 2000 ).…”

Neuropeptidergic control circuits in the spinal cord for male sexual behaviour: Oxytocin–gastrin‐releasing peptide systems

“…Bombesin and GRP were earlier considered orthologous among frogs and mammals. However, it is reported that in frogs, GRP exists separately from bombesin, suggesting that GRP is not a mammalian bombesin 25,26 . GRP is highly expressed in the hippocampus, 11 lateral amygdala, 11 accessory basal nucleus of the amygdala, 27 suprachiasmatic nucleus, 8 dorsomedial nucleus of the hypothalamus, 28 and dorsal root/trigeminal ganglion neurons 29 .…”

A non-canonical retina-ipRGCs-SCN-PVT visual pathway for mediating contagious itch behavior

“…Gastrin-releasing peptide (GRP) in somatosensory neurons encodes itch-specific information and can activate GRPR, a G q protein-coupled receptor (GPCR), in the spinal cord to transmit itch information in mice ( Barry et al, 2020 ; Chen, 2021 ; Sun and Chen, 2007 ; Sun et al, 2009 ). GRP is conserved across animal phyla, including mammals ( Hirooka et al, 2021 ; Takanami et al, 2022 ). Suprachiasmatic nucleus (SCN) GRP neurons are a subset of retinorecipient cells located in the ventrolateral side (the core area) and convey photic information directly from the retinohypothalamic tract (RHT) ( Abrahamson and Moore, 2001 ; Karatsoreos et al, 2004 ).…”