title: Facilitation of acetylcholine release by SK-951, a benzofuran derivative, via the 5-hydroxytryptamine4 receptor in guinea pig stomach.
abstract: Facilitation of acetylcholine (ACh) release by SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0] octan-5-yl)ethyl]-5-chloro-2,3-dihydro-2-methylbenzo[b]furan-7-carboxami de hemifumarate), a benzofuran derivative, via the 5-hydroxytryptamine (5-HT)4 receptor in guinea pig stomach was examined by in vitro receptor autoradiography and functional studies. [125I]SB207710 binding was detected in the myenteric plexus of the gastric corpus. High densities of binding sites were observed in the myenteric plexus and a moderate density in the muscle layer. SK-951 inhibited the binding of [125I]SB207710, a specific 5-HT4-receptor ligand, as in the case of SB204070, a specific 5-HT4-receptor antagonist, thus indicating the presence of 5-HT4 receptors in guinea pig stomach. SK-951 as well as 5-HT enhanced the electrically stimulated twitch contractions of gastric corpus strips, which were sensitive to tetrodotoxin and atropine, and enhanced electrically stimulated release of ACh from corporal strips, which was tetrodotoxin-sensitive and Ca2+-dependent. The enhancements of twitch contractions and ACh release by SK-951 were antagonized by GR113808, a selective 5-HT4-receptor antagonist. Thus, SK-951 binds to 5-HT4 receptors of the guinea pig gastric corpus and may accelerate gastric motility due to facilitation of ACh release.
authors.affiliation: Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai-Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Taniyama
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004146:Dioxanes / Q000378:metabolism; D004558:Electric Stimulation; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010880:Piperidines / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D005765:Gastrointestinal Agents; D010880:Piperidines; D011985:Receptors, Serotonin; C088873:SB 207710; C113458:SK 951; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D000109:Acetylcholine