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Peptide and Protein Hormones ------9. Motilin [2005]

Author:N/A    | Post time:2012-05-26

9. Motilin [2005]
Top of page
1. Introduction
2. Gonadoliberin, Thyroliberin, Gonadotropins, Thyrotropin, Inhibin, and Related Hormones
3. Parathyroid Hormone and the Calcitonin Family
4. Corticoliberin – Proopiomelanocortin Cascade
5. Blood Pressure Regulating Peptides
6. Cholecystokinin and Gastrin
7. Secretin Family
8. Neurotensin [1971]
9. Motilin [2005]
10. Pancreatic Spasmolytic Peptide
  Occurrence. p-Motilin (MT) [9072-41-7], Mr 2699.1 (h-MT), is a peptide containing 22 amino acids. The precursor of h-MT has been characterized via the cDNA [2006].

Motilin is found primarily in the jejunum but immunoreactive motilin has also been found in the mucosa of the esophagus, stomach, duodenum, ileum, and colon, in the pancreas, kidneys, adrenals, gallbladder, and brain.

Erythromycin A [2007] and the erythromycin derivative EM-523 [2008] are macrolide antibiotics which greatly increase the gastrointestinal motor activity and are motilin receptor agonists.

  Release. The release of motilin is stimulated by oral fat, exogenous and endogenous bile acids, bombesin, alkalization of the duodenum (in the dog), acidification of the duodenum (in humans and pigs), stimulation of the vagus, exogenous motilin, and atropine [2009].

Release is inhibited by oral glucose, insulin, somatostatin, pancreatic peptide, VIP, and by sham feeding [2010].

In humans, elevated levels of MT have been observed in diarrhoea, kidney failure, after abdominal surgery and in alcoholics who do not have liver disease [2011].

  Biological Effects. Motilin increases smooth muscle Ca2+ transport and stimulates intracellular cGMP synthesis. On a molar basis, motilin has 50 times the contracting effect of acetylcholine in the duodenum.

The motilins appear to be species specific [2012]. Motilin induces contraction of the gastrointestinal tract and accelerates gastric emptying and intestinal transit. MT also contracts the lower esophageal sphincter and the gallbladder, and activates the Oddi sphincter [2013]. The cyclic pancreatic secretion of water, bicarbonate, and protein is increased by MT [2014].

In fasting rats, intraperitoneally applied MT (5 – 10 µg/kg) increases food uptake. This effect can be abolished by naloxone or pentagastrin. Thus, MT appears to be responsible for hunger during fasting [2015]. An infusion of low doses of motilin accelerates the absorption of glucose, increasing the plasma levels of glucose, GIP, and insulin. An infusion of high doses of motilin has the opposite effect.

Structure – Activity Relationships. p-MT-(1 – 16) has 3 % of the p-MT activity (contraction of duodenum). Gly8 can be replaced by d-Ala without loss of activity (i.e., contraction of the duodenum); Met13, Gln14, and Glu15 do not appear to be important for biological activity [2016], whereas substitution of Ser or Lys for Phe1 produces compounds that are 250 and 1000 times less active, respectively [2017].

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