title: Geissoschizine methyl ether, an indole alkaloid extracted from Uncariae Ramulus et Uncus, is a potent vasorelaxant of isolated rat aorta.
abstract: Effects of geissoschizine methyl ether, an indole alkaloid isolated from the hook of Uncariae Ramulus et Uncus, on vascular responses were examined using isolated strips of rat aorta. Geissoschizine methyl ether (10(-7)-10(-4) M) relaxed norepinephrine (5x10(-8) M)-induced contraction in a dose-dependent manner. The potency (50% efficacy concentration, EC(50)=0.744 microM) was approximately 14 times greater than that (EC(50)=10.6 microM) of hirsutine, one of the indole alkaloids isolated from Uncariae Ramulus et Uncus that demonstrates a vasorelaxant effect by Ca(2+)-channel blocking. The vasorelaxant effect of geissoschizine methyl ether found at the lower concentrations (10(-7)-3x10(-6) M) on the norepinephrine-induced contraction was abolished by pretreatment with N(G)-nitro-L-arginine (10(-4) M), an inhibitor of nitric oxide synthesis, or by denuding aortas of endothelium, while the effects at the higher concentrations (10(-5)-10(-4) M) were not completely prevented by either N(G)-nitro-L-arginine and deendothelialization. Furthermore, geissoschizine methyl ether did not relax high K(+)-, Ca(2+)- and a Ca(2+)-channel agonist Bay K8644-induced contractions at the lower concentrations that markedly relaxed the norepinephrine-induced contractions, while the higher concentrations of geissoschizine methyl ether relaxed the high K(+)-, Ca(2+)- and Bay K8644-induced contractions. These results suggest that the vasorelaxant effect of geissoschizine methyl ether is composed of two different mechanisms: endothelial dependency with nitric oxide and endothelial independency with voltage-dependent Ca(2+)-channel blocking.
authors.affiliation: Kampo & Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun 3586, Ibaraki 300-1192, Japan. yuzurihara_mitsutosh@mail.tsumura.co.jp
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yuzurihara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Goto
authors.forename: Iwao
authors.initials: I
authors.lastname: Sakakibara
authors.forename: Terumasa
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D032070:Uncaria / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D026121:Indole Alkaloids; D007211:Indoles; D010936:Plant Extracts; C110832:geissoschizine methylether