Enhancement by KW-5092, a Novel Gastroprokinetic Agent, of the Release of Acetylcholine from Enteric Neurons in the Guinea Pig Ileum

The Japanese Journal of Pharmacology

Nobuyuki Kishibayashi¹  Akio Ishii¹  Akira Karasawa¹ 

[1] Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.

关键词: KW-5092;    Ileum (guinea pig);    Acetylcholine release;    Myenteric plexus;   

DOI  :  10.1254/jjp.64.289

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(10)Cited-By(12)KW-5092 ({1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2-imidazolidinylidene} propanedinitrile fumarate) is a novel gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory activity. The present study examined the effects of KW-5092 on intestinal contraction and on acetylcholine (ACh) release in the isolated longitudinal muscle-myenteric plexus preparation of guinea pig ileum. In the electrically stimulated preparation, KW-5092 enhanced the contraction at 10-9 M to 3 × 10-6 M and potentiated the ACh release at 10-8 M to 3 × 10-6 M. In the unstimulated preparation, KW-5092 at 10-8 M to 10-4 M evoked the contraction and ACh release. Both the contraction and the ACh release by KW-5092 were abolished by tetrodotoxin (10-7 M) or removal of external Ca2+, and the evoked contraction was abolished by atropine (10-7 M). The ACh release by KW-5092 was not affected by hexamethonium (3 × 10-5 M), suggesting that the nicotinic receptor is not involved in the ACh release. Neostigmine, whose AChE inhibitory activity is equipotent to that of KW-5092, did not evoke ACh release even at 3 × 10-6 M, indicating that the ACh release by KW-5092 is not due to its AChE inhibitory activity. The present results suggest that KW-5092 evokes ACh release by stimulating a cholinergic pathway and that the ACh release by KW-5092 may contribute to its gastroprokinetic effects.

【 授权许可】

Unknown