Facilitation of Acetylcholine Release by SK-951, a Benzofuran Derivative, via the 5-Hydroxytryptamine_4 Receptor in Guinea Pig Stomach

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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-carboxamine 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.
社団法人日本薬理学会の論文
2000-02-01