Motilin in amphibians.

Motilin was first identified as a gastrointestinal (GI) motility-stimulating peptide and was later shown to mediate the gastric migrating motor complexes (MMCs) in several mammals. Motilin and its receptor have also been identified in non-mammalian vertebrates, including birds, reptiles, amphibians and fish. This discovery has prompted comparative studies on its physiological roles in GI motility. This review focused on amphibian motilin and its role in GI contractions. Like those of mammals, birds, and reptiles, amphibian motilin is a 22-amino-acid peptide produced in the mucosa of the upper small intestine. There is structural variation within amphibians: the N-terminal residue is phenylalanine in Caudata (newts and salamanders) but tyrosine in Apoda (caecilians). Interestingly, motilin receptors have been found in Anura (frogs), yet the endogenous motilin remains undiscovered, even though database searches. This discrepancy leaves the physiological role of the motilin system in anurans a subject of ongoing debate. Functional studies reveal that motilin receptors exist in the central nervous system and the GI tract of vertebrates, and demonstrate an evolutionarily related shift in localization. Motilin receptors are restricted to intestinal mucosal cells in fish but expand to GI smooth muscle cells and enteric neurons in amphibians. This marks a pivotal transition toward the regulation of GI motility. This trajectory culminates in birds and mammals, where receptors are present across the mucosa, smooth muscle, and myenteric plexus. However, the mechanisms driving this receptor expansion, the definitive status of motilin in Anuras, and the specific roles of motilin receptor or motilin-like receptor in these species remain unclear. Addressing these questions will provide deeper insights into the evolutionary endocrinology of the gut-brain axis, establishing amphibian motilin research as a compelling frontier.