ABSTRACT
SK-896 [(Leu(13))motilin-Hse] is a new human motilin analogue synthesized from Escherichia coli using a biotechnological method. We investigated the gastrointestinal motor-stimulating effect of SK-896 and the mechanism of this effect using implanted force transducers in conscious dogs. Infusion of SK-896 during phase I in the interdigestive state induced interdigestive migrating contractions like motility in the gastroduodenum. The motility index (MI(0-20)) of gastric antrum motor activity induced by SK-896 was increased dose dependently (r = 0.830, p < 0.001), and the MI(0-20) induced by SK-896 at a dose of 0.25 microg/kg/h for 20 min was the same as that for spontaneous phase III contractions. The SK-896-induced MI(0-20) was significantly decreased by atropine, hexamethonium, dopamine, granisetron, and yohimbine. Conversely, ketanserin, phentolamine, timolol, and naloxone did not have significant effects on SK-896-induced MI(0-20). The effects of these drugs on human motilin (0.25 microg/ kg/h for 20 min) induced MI(0-20) were the same as those of SK-896. These results indicate that SK-896 induces gastrointestinal motility during the interdigestive period in dogs with regulation of acetylcholine release from the cholinergic nerve terminal via the parasympathetic nervous system in the same fashion as human motilin.
Subject(s)
Digestion/drug effects , Gastrointestinal Motility/drug effects , Motilin/analogs & derivatives , Motilin/pharmacology , Animals , Digestion/physiology , Dogs , Dose-Response Relationship, Drug , Gastrointestinal Motility/physiology , Humans , Male , Muscarinic Agonists/pharmacology , Muscarinic Antagonists/pharmacology , Pyloric Antrum/drug effects , Pyloric Antrum/physiology , SwineABSTRACT
The aim of this study was to investigate the effect of SK-896 (Phe-Val-Pro-Ile-Phe-Thr-Try-Gly-Glu-Leu-Gln-Arg-Leu-Gln-Glu-Lys-Glu- Arg-Asn-Lys-Gly-Gln-Hse), a new motilin analogue, on gastrointestinal motility and transit in dogs with post-operative ileus, and to compare the effects of this agent on these parameters with the effects of prostaglandin F(2alpha), a well-known gastroprokinetic agent. We used chronically implanted force transducers to measure motility and radiography of radio-opaque markers to measure transit. Infusion of SK-896 1 microgram/kg/h, for 20 min twice a day induced interdigestive migrating contractions-like motility. Infusion of prostaglandin F(2alpha), 20 microgram/kg/h, for 1 h twice a day induced continuous contractions in the distal part of the small intestine. The time of first appearance of interdigestive migrating contractions in the stomach (gastric-interdigestive migrating contractions) and the gastric emptying time of the solid marker with the administration of SK-896 were significantly less than those noted with the administration of prostaglandin F(2alpha). It appears that gastric-interdigestive migrating contractions play an important role in the transit of substances, especially solid substances, in the gastrointestinal tract. We conclude that SK-896, which induced gastric-interdigestive migrating contractions, is effective to induce early recovery from post-operative ileus.
Subject(s)
Intestinal Obstruction/prevention & control , Motilin/pharmacology , Postoperative Complications/prevention & control , Amino Acid Sequence , Animals , Digestive System/drug effects , Digestive System/physiopathology , Digestive System Surgical Procedures , Dogs , Gastrointestinal Motility/drug effects , Gastrointestinal Transit/drug effects , Intestinal Obstruction/etiology , Intestinal Obstruction/physiopathology , Male , Molecular Sequence Data , Motilin/analogs & derivatives , Myoelectric Complex, Migrating/drug effects , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Time FactorsABSTRACT
1. The HCl-methanol (HCl-MeOH) soluble fraction from the puparial cuticle of yellow, black and ebony of D. melanogaster was hydrolyzed in hydrochloric acid and examined for beta-alanine, ketocatechol, and acetic acid. 2. Between beta-alanine and ketocatechol and between beta-alanine and acetic acid, a quantitatively inverse relationship was found, respectively. The former relationship was further confirmed by the feeding experiment of beta-alanine to black. 3. Of total beta-alanine in the HCl-MeOH extract, the proportion of those having free amino group was 74.8 per cent. 4. All these results indicate that the HCl-MeOH soluble fraction of the puparial cuticle may be useful for investigating the cross-link structure of the cuticle.
