Ghrelin Peptide Does Not Control Gut Movement in Frogs and Newts, Revealing Surprising Evolutionary Diversity in Peptide Function

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.

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.

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.

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.