title: Effects of geissoschizine methyl ether, an indole alkaloid in Uncaria hook, a constituent of yokukansan, on human recombinant serotonin 7 receptor.
abstract: Effects of seven alkaloids, geissoschizine methyl ether (GM), hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine and isocorynoxeine, in Uncaria hook, a constituent of the kampo medicine yokukansan, on serotonin(7) (5-HT(7)) receptor were investigated using Chinese hamster ovary (CHO) cell membranes and human embryonic kidney 293 (HEK293) cells stably expressing the human recombinant 5-HT(7) receptor. A competitive binding assay using CHO membranes showed that GM (IC(50) = 0.034 μM) more strongly inhibited the binding of the radioligand [(3)H] LSD to 5-HT(7) receptor than the other alkaloids, suggesting that GM is bound to 5-HT(7) receptor. Agonistic/antagonistic effects of GM (1-50 μM) on the receptor were evaluated by measuring intracellular cAMP levels in HEK239 cells. GM (IC(50) = 6.0 μM) inhibited 5-HT-induced cAMP production in a concentration-dependent manner, as well as the specific 5-HT(7) receptor antagonist SB-269970 (0.1-1 μM). However, GM did not induce intracellular cAMP production as 5-HT did. These results suggest that GM has an antagonistic effect on 5-HT(7) receptor.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan. ueki_toshiyuki@mail.tsumura.co.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ueki
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Imamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kanno
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Kyoji
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D032070:Uncaria
chemical_list: D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D007211:Indoles; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; C524644:Yi-Gan San; C110832:geissoschizine methylether; C104425:serotonin 7 receptor