Gastroprokinetic effect and mechanism of SK-896, a new motilin analogue, during the interdigestive period in conscious dogs

Citation
K. Tsukamoto et al., Gastroprokinetic effect and mechanism of SK-896, a new motilin analogue, during the interdigestive period in conscious dogs, PHARMACOL, 63(2), 2001, pp. 95-102
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOLOGY
ISSN journal
0031-7012 → ACNP
Volume
63
Issue
2
Year of publication
2001
Pages
95 - 102
Database
ISI
SICI code
0031-7012(2001)63:2<95:GEAMOS>2.0.ZU;2-X
Abstract
SK-896 [(Leu(13))motilin-Hse] is a new human motilin analogue synthesized f rom Escherichia coli using a biotechnological method. We investigated the g astrointestinal motor-stimulating effect of SK-896 and the mechanism of thi s effect using implanted force transducers in conscious dogs. Infusion of S K-896 during phase I in the interdigestive state induced interdigestive mig rating contractions like motility in the gastroduodenum. The motility index (MI0-20) of gastric antrum motor activity induced by SK-896 was increased dose dependently (r = 0.830, p < 0.001), and the MI0-20 induced by SK-896 a t a dose of 0.25 mug/kg/h for 20 min was the same as that for spontaneous p hase III contractions. The SK-896-induced MI0-20 was significantly decrease d by atropine, hexamethonium, dopamine, granisetron, and yohimbine. Convers ely, ketanserin, phentolamine, timolol, and naloxone did not have significa nt effects on SK-896-induced MI0-20. The effects of these drugs on human mo tilin (0.25 mug/kg/h for 20 min) induced MI0-20 were the same as those of S K-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. Copyright (C) 2001 S. Karger AG, Base.