Motilin Sequences、胃動素序列

Definition

Motilin is a hormone produced from endocrine cells of the duodenal mucosa to help regulate motility of the digestive tract.

Discovery

Motilin was discovered by Brown when he introduced alkaline solution into duodenum of dogs which caused strong gastric contractions. Brown et al,. predicted that alkali could either release stimulus to activate motor activity or prevent the secretion of inhibitory hormone. They isolated polypeptide as a byproduct from purification of secretin on carboxymethyl cellulose. They named this polypeptide “Motilin” 1.

Structural characteristics

Motilin has 22 amino acids and molecular weight of 2.6 kDa. The motilin gene has an unusual structure in which a small bioactive peptide is encoded on two distinct exons. Examination of the expression of the human and nonhuman primate motilin gene by Northern hybridization analysis indicates that it is expressed in a number of gastrointestinal and extragastrointestinal tissues 2. The sequences of amino acids of motilin is: Phe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln. The 13C dynamics clearly show that motilin has a large degree of local flexibility and interacts with the bicelle, displaying motional properties of a peptide bound to a membrane. In comparison, motilin in neutral bicelles seems less structured and more flexible. The structure reveals an ordered alpha-helical conformation between Glu-9 and Lys-20. The N-terminus is also well structured with a turn resembling that of a classical beta-turn 3.

Mode of Action

Motilin is a member of the peptide family that includes ghrelin whose cDNA also encodes peptide, obestatin. Motilin is a fascinating hormone for the physiologist. It interacts with the family member ghrelin and with obestatin. Motilin-receptor agonists or antagonists could soon be part of the therapeutic arsenal of the clinician to improve digestive dysmotility 4. The influence of the vagus on the circulating levels of immunoreactive (IR) motilin was also determined. Five mongrel dogs were equipped with chronically implanted electrodes in the small intestine to record the myoelectrical activity. The release of IR motilin during fasting, after a meal, and during an infusion of insulin was studied before and after truncal vagotomy at the diaphragmatic level. When tested at least two weeks after the operation, the motility pattern of the small intestine and the secretion of IR motilin remained unaltered by vagal section. Cyclic increases in IR motilin associated with phase III's of the interdigestive myoelectric complexes were still observed after vagotomy, and they were still abolished by feeding or by insulin. The release of motilin is not chronically altered by distal vagotomy in dogs 5.

Functions

The main function of motilin is to increase the migrating myoelectric complex component of gastrointestinal motility and stimulate the production of pepsin. A high level of motilin secreted between meals into the blood, stimulates the contraction of the fundus and antrum and accelerates gastric emptying. It then contracts the gallbladder and increases the squeeze pressure of the lower esophageal sphincter. Motilin increases the release of pancreatic polypeptide and somatostatin 6. Both the vagus nerve and motilin have been implicated in the initiation of phase III of the fasting migrating motor complex. Intralumenal pressures of the lower esophageal sphincter, stomach, and upper small intestine, and plasma motilin levels were monitored. Results in dogs indicate that while spontaneous phase II motility in the upper gastrointestinal tract and phase III activity in the lower esophageal sphincter and stomach are dependent on vagally mediated excitatory pathways, spontaneous and induced phase III motor activity in the small intestine are dependent on nonvagal cholinergic innervation. Canine motilin release induced by porcine motilin is mediated primarily by a nonvagal cholinergic (muscarinic) pathway, with minor contributions from vagal noncholinergic, and nonvagal noncholinergic mechanisms. Motilin may modulate motility produced by preexisting neural excitation   7.

References

1.Brown JC, Cook MA, Dryburgh JR (1973). Motilin, a gastric motor activity stimulating polypeptide: the complete amino acid sequence. Canadian journal of biochemistry, 51(5): 533–557.

2.Daikh DI, Douglass JO, Adelman JP (1989). Structure and expression of the human motilin gene. DNA., 8 (8):615–621.

3.Andersson A, Mäler L (2002). NMR solution structure and dynamics of motilin in isotropic phospholipid bicellar solution. J. Biomol NMR., 24 (2):103–112.

4.Poitras P, Peeters TL (2008).Motilin. Curr Opin Endocrinol Diabetes Obes., 15(1):54–57.  

5.Lemoyne M, Wassef R, Tassé D, Trudel L, Poitras P (1984). Motilin and the vagus in dogs. Canadian journal of physiology and pharmacology., 62(9):1092–1096.

6.Book: Williams, Robert L. (1981). Textbook of endocrinology., (6th ed.). Philadelphia: Saunders.

7.Hall KE, Greenberg GR, El-Sharkawy TY, Diamant NE (1984). Relationship between porcine motilin-induced migrating motor complex-like activity, vagal integrity, and endogenous motilin release in dogs. Gastroenterology, 87 (1): 76–85.