Unlike in mammals and birds, the gut peptide ghrelin had no effect on gastrointestinal smooth muscle contraction in bullfrogs or newts, while motilin — another peptide — was shown for the first time to stimulate gut contractions in amphibians.
Zero gut motility effectGhrelin from multiple sources had no effect on gastrointestinal contraction in either amphibian species, despite confirmed receptor expression
What the researchers found
Neither bullfrog ghrelin nor rat ghrelin affected longitudinal smooth muscle contractility of gastrointestinal strips from bullfrogs or Japanese fire belly newts. The ghrelin receptor (GHS-R1a) mRNA was confirmed present in the bullfrog GI tract, with higher expression in intestinal mucosa than gastric mucosa — yet the receptor did not mediate contractile responses.
Other gastrointestinal peptides including substance P, neurotensin, and motilin, plus the muscarinic agonist carbachol, all induced marked contractions, confirming the muscle preparations were functional. This was the first demonstration that motilin induces gastrointestinal contraction in amphibians. The results parallel findings in fish (rainbow trout, goldfish) where ghrelin also lacks gut motility effects, but contrast with mammals and birds where ghrelin is a potent gut motility regulator.
Why it matters
Understanding how peptide hormones evolved different functions across species is fundamental to peptide biology. The finding that ghrelin — one of the most studied gut peptides — has completely different gastrointestinal effects in different vertebrate classes cautions against assuming universal peptide function. For drug development, this highlights that peptide receptors being present does not guarantee functional responses, and that animal model selection for peptide drug testing requires careful consideration of species-specific physiology.
How the study worked
In vitro smooth muscle contractility experiments using isolated longitudinal gastrointestinal strips from bullfrogs (Rana catesbeiana) and Japanese fire belly newts. Ghrelin (species-matched and rat-derived), motilin, substance P, neurotensin, and carbachol were applied to muscle preparations. GHS-R1a receptor mRNA expression was quantified in bullfrog gastrointestinal tissues.
What this study cannot tell us
The study used in vitro isolated muscle strips, which may not fully represent in vivo conditions where neural and hormonal factors interact. Only longitudinal muscle contractility was tested; circular muscle responses may differ. The specific sample sizes (number of animals) are not detailed. Only two amphibian species were tested, limiting generalization. The study did not investigate whether ghrelin might affect other GI functions (secretion, blood flow) in amphibians through non-contractile pathways.
How to read the evidence
This is a well-controlled in vitro comparative physiology study. The use of positive controls (substance P, carbachol) confirming muscle preparation viability, receptor mRNA verification, and testing across two species provides solid evidence for the negative finding. However, it is limited to two species and one functional assay.
When this study was published
Published in 2016, this study remains relevant as a key reference for understanding the evolutionary diversity of ghrelin function across vertebrates.
The bigger picture
This study contributes to the evolutionary pharmacology of gut peptides, revealing that ghrelin's role in gastrointestinal motility is not conserved across vertebrates. The pattern that emerges — ghrelin regulates gut motility in mammals and birds but not in fish or amphibians — suggests this function evolved relatively recently in vertebrate history. Meanwhile, motilin appears to have a more ancient and conserved role in gut contraction. These evolutionary insights inform our understanding of peptide signaling system evolution and have practical implications for choosing appropriate animal models in peptide research.
Questions still open
- Why did the ghrelin receptor evolve to be expressed in amphibian gut tissue if it doesn't regulate motility — does it serve another function there?
- At what point in vertebrate evolution did ghrelin acquire its gut motility-regulating function?
- Does motilin have a conserved gut motility role across all vertebrate classes, potentially making it a more universal drug target?
Common questions
Why doesn't ghrelin work the same way in all animals?
What is motilin and why is its discovery in amphibians important?
Read the original research
Effects of ghrelin and motilin on smooth muscle contractility of the isolated gastrointestinal tract from the bullfrog and Japanese fire belly newt.
General and comparative endocrinology, 232, 51-9
Citation
Kitazawa, Takio; Shimazaki, Misato; Kikuta, Ayumi; Yaosaka, Noriko; Teraoka, Hiroki; Kaiya, Hiroyuki. (2016). Effects of ghrelin and motilin on smooth muscle contractility of the isolated gastrointestinal tract from the bullfrog and Japanese fire belly newt.. General and comparative endocrinology, 232, 51-9. https://doi.org/10.1016/j.ygcen.2015.12.013