Disease relevance of MLN

• 1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs [1].
• The role of motilin in the periodic interdigestive secretion of the pancreas was studied in conscious dogs, each with a chronic gastric fistula, a Heidenhain pouch and a Thomas duodenal fistula [2].
• These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth [3].
• Octreotide ameliorated the ileus and restored the cyclic increases in motilin found in health, nor did it alter plasma substance P and VIP [4].
• Motilin and secretin were compared in regard to their effects on pancreatic bicarbonate and protein secretion in conscious dogs provided with chronic pancreatic fistulas [5].

Psychiatry related information on MLN

• Relationships among canine interdigestive exocrine pancreatic and biliary flow, duodenal motor activity, plasma pancreatic polypeptide, and motilin [6].
• The effect of cisplatin on interdigestive myoelectric activity (IDMA) of the gastric antrum, duodenum and jejunum, plasma concentration of motilin, and animal behavior was studied in seven conscious dogs with gastric cannulas and platinum electrodes implanted on the serosal surface of antrum and upper small intestine [7].

High impact information on MLN

• When synthetic somatostatin, a known inhibitor of endogenous motilin release, was infused at a rate that raised the plasma SLI to approximately the levels observed during the contraction period (0.1 microgram/kg per h), the appearance of the subsequent GIC was significantly delayed [8].
• Atropine abolished motilin-induced gastric contractions, secretion, and phasic changes of LGA blood flow but failed to affect the sustained flow increase [9].
• The LGA flow responses to motilin were not inhibited by granisetron, C6, alpha-adrenergic, beta-adrenergic, or H2 blockers [9].
• Motilin induced significantly larger gastric vasodilatation than the equivalent doses of VIP [9].
• Motilin was infused intravenously with or without Phe-cyclo[Lys-Tyr(3-tBu)-betaAla-]. trifluoroacetate (GM-109; motilin antagonist), granisetron (5-HT3 antagonist), atropine, hexamethonium (C6), phenoxybenzamine, propranolol, or cimetidine [9].

Chemical compound and disease context of MLN

• In both intact and vagally blocked dogs, atropine abolished both the spontaneous motor activity and associated rise in motilin level, and also abolished porcine motilin-induced activity [10].
• These changes in both motility and plasma motilin levels may play a part in the mechanism of emesis induced by cisplatin in dogs [7].
• The latter hypothesis is supported by the observation that motilin had no effect on the motor activity of the small intestine during the infusion of pentagastrin which abolishes spontaneous migrating myoelectric complexes [11].
• These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers [12].

Biological context of MLN

• The vagus, motilin, and the migrating motor complex [13].
• Effects of corticotropin-releasing factor on plasma motilin and somatostatin levels and gastrointestinal motility in dogs [14].
• Motilin enhances gastric emptying of liquids in dogs [15].
• BACKGROUND & AIMS: EM523, a motilin agonist, is intended to be used as a gastroprokinetic during the postprandial period, but the mechanism(s) by which EM523 stimulates postprandial contractions in the stomach has not been studied before [16].
• The docosapeptide and the tritetracontapeptide corresponding to the entire amino acid sequence of porcine motilin and gastric inhibitory peptide were synthesized, and in addition, an unsulfated form of cholecystokinin-pancreozymin (CCK-PZ) was prepared to cast some light on the structure-activity relationships of these gastrointestinal hormones [17].

Anatomical context of MLN

• This study suggests that the duodenum plays an important role in the initiation of the gastric migrating motor complex and in the coordination of interdigestive gastrointestinal motor activity, possibly by the release of motilin [18].
• The effect of morphine and motilin on surgically isolated segments of small intestine was studied in 8 dogs [19].
• The effects of intracerebroventricular and intravenous administration of corticotropin-releasing factor (CRF) on gastrointestinal motility, motilin-induced gastric motor response, and plasma motilin and somatostatin levels were investigated in fasted dogs chronically prepared with strain gauge transducers on the antrum and proximal jejunum [14].
• Comparison of gallbladder contractions induced by motilin and cholecystokinin in dogs [20].
• Intralumenal pressures of the lower esophageal sphincter, stomach, and upper small intestine, and plasma motilin levels were monitored [10].

Associations of MLN with chemical compounds

• The results suggest that cholinergic pathway, 5-hydroxytryptamine (HT)3 receptors, and alpha receptors are involved in the motilin-induced contractions [21].
• The contraction generated by synthetic canine motilin (10(-5) M) was not influenced by atropine, hexamethonium, tetrodotoxin, naloxone, or sodium nitroprusside (all used at 10(-4) M) but was blocked by verapamil (10(-4)) [22].
• In conclusion, the present findings suggest the possible involvement of 5-hydroxytryptamine 3 receptors on vagal afferents especially in terms of endogenous release of acetylcholine in the control of interdigestive phase III activity in the stomach by motilin [23].
• CONCLUSIONS: EM-523-induced phase III-like contractions are brought about through the cholinergic neural pathway and 5-HT3 receptors, and endogenous motilin release is partially involved [24].
• Atropine, hexamethonium, ICS205-930, BRL43694, phentolamine, yohimbine, and propranolol significantly inhibited motilin-induced contractions [21].

Regulatory relationships of MLN

• Modulation of motilin-induced somatostatin release in dogs by naloxone [25].

Other interactions of MLN

• RESULTS: A single injection of EM523 always induced phase III-like contractions in the intact gastric antrum and was accompanied by significant (P < 0.01) release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin, cholecystokinin, and secretin were not released by EM523 [26].
• In addition, serum levels of motilin and PYY were determined before and during the administration of 1500 cGy in four separate dogs instrumented to record upper gut contractile activity [27].
• No immunoreactive neurons were observed with the available antisera to galanin, gastrin-releasing peptide, and motilin [28].

Analytical, diagnostic and therapeutic context of MLN

• Porcine and canine motilin in plasma were distinguished by radioimmunoassay using two different antibodies [10].
• Effect of central sympathectomy on gastric and small intestinal myoelectric activity and plasma motilin concentrations in the dog [29].
• Pancreatectomy led to undetectable plasma concentrations of pancreatic polypeptide, but had no effect on absolute concentrations of plasma motilin or on the cycling of plasma motilin in association with the duodenal migrating motor complex [30].
• Intravenous infusion of PG (4 micrograms/kg-hr) inhibited motilin-induced phase III activity both in the main stomach and in the HP, whereas histamine (40 micrograms/kg-hr) inhibited activity only in the main stomach [31].
• Before and after vagotomy, motilin and insulin induced a premature MMC with minor changes in contractile pattern [32].

References