KW-5092, a novel gastrokinetic agent, facilitates luminal serotonin release from the guinea-pig colon.
The present study was designed to determine the influence of KW-5092 ((1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2- imidazolidinylidene) propanedinitrile fumarate), a novel gastroprokinetic agent on intraluminal serotonin (5-hydroxytryptamine, 5-HT) release which reflects the release of 5-HT from enterochromaffin cells, using the luminally perfused isolated guinea-pig proximal colon in vitro. 5-HT was determined by high-performance liquid chromatography with electrochemical detection. KW-5092 (1-10 microM) concentration-dependently caused an increase in the luminal 5-HT outflow. In the presence of atropine (0.2 microM) or tetrodotoxin (0.3 microM), the stimulatory action of KW-5092 (10 microM) was inhibited by 94% and 74%, respectively. These results suggest that KW-5092 stimulates intraluminal 5-HT release from luminally perfused proximal colon of the guinea-pig via the stimulation of cholinergic neurons. Because 5-HT is recognized as an important messenger substance in the control of intestinal motility, this stimulatory effect could be considered as an indirect action of KW-5092 that may contribute to its prokinetic effects.
Kojima
S
S
Department of Pharmacology, Dokkyo University School of Medicine, Mibu, Japan. s-kojima@dokkyomed.ac.jp
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D005765:Gastrointestinal Agents; D007093:Imidazoles; D009570:Nitriles; C081341:KW 5092; D012701:Serotonin; D013779:Tetrodotoxin; D001285:Atropine