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
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.