Gastroprokinetic effect and mechanism of SK-896, a new motilin analogue, during the interdigestive period in conscious dogs.
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.
Tsukamoto
K
K
Central Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Inabe-gun, Mie, Japan. k_tsukamoto@mb4.skk-net.com
Tagi
Y
Y
Nakazawa
T
T
Takeda
M
M
D000818:Animals; D004063:Digestion / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D009037:Motilin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology; D013552:Swine
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; C414785:SK896; D009037:Motilin