Motilin is secreted by M cells present in the duodenum and proximal jejunum. Motilin has 22 amino acids and has no identifiable sequence homology with other gastrointestinal hormones; see Figure 1A. Figure 2B illustrates the 22 amino acids of motilin in solution in a ribbon structure as elucidated by NMR analysis. Motilin does not have a long-enough amino acid sequence to utilize the pancreatic polypeptide fold. The PP fold of the 36 amino acid pancreatic polypeptide is shown in Figure 3.
Fig1. Motilin’s amino acid sequence and its three-dimensional ribbon structure. (A) Amino acid sequence of motilin. (B) NMR solution structure of motilin. The 22 amino acid sequence of motilin in solution assumes a ribbon structure.
Fig2. Amino acid sequences of calcitonin gene-related peptide (CGRP) and amylin. (A) The CGRP and the related peptide, amylin, are both members of the family of calcitonin-gene-related peptide and related peptides. Both peptides, CGRP and amylin, have 37 total amino acids. Of the 37 amino acids of CGRP and amylin, 17 (45%) are colored gold marking the identical amino acid positions in these two peptides. (B) Both peptides have a 6-amino acid ring structure created by the disulfide bond occurring between cysteine #2 and #7. Both peptides have a 6-amino acid ring structure created by the disulfide bond occurring between cysteine #2 and #7.
Fig3. Amino acid sequence comparison of the pancreatic polypeptide hormone family. These include pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and neuropeptide tyrosine (NPY). (A) The 36 amino acids of each of the hormones are colored differently; PP is blue, PYY is purple, and NPY is green. The three peptides were aligned on the basis of each of the NH2-terminus residues being assigned #1 and the carboxy amide being numbered 36. Each of the 36 amino acid residues of PP was separately compared with the 36 residues of PYY and NPY. All exact matches with PP were colored gold. Also, the amino acid sequences of PYY and NPY were compared and all identical amino acid identities were also colored gold. These matches may reflect evolutionary changes in the order of amino acids. (B) Illustration of the pancreatic polypeptide fold as determined via x-ray crystallography and also NMR. The PP fold is comprised of residues #3 to #31 of the 36 amino acid peptide. The formation of the “fold” is believed to be facilitated by the four proline residues at peptide positions #2, #5, #8, and #14.
A major role of motilin in the stomach is to stimulate the production of pepsin which, in turn, will stimulate the contraction of the fundus and antrum so as to accelerate gastric emptying. Additionally motilin stimulates gallbladder contractions. Also, motilin is believed to play a role in the stimulation of small intestinal motility during fasting. Its release from the endocrine enterochromaffin-like (ECL) cells of the duodenum is cyclical, occurring approximately every 2 hr. Significantly, most of motilin’s actions do not coincide with dietary intake, but with fasting. It has been suggested that this enhances the movement of digested food particles in preparation for the next meal. The physiological role of motilin remains to be clarified.
