| In vitro: |
| Neuroscience. 2012 Apr 5;207:124-36. | | Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin ₁A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan.[Pubmed: 22314317 ] |
METHODS AND RESULTS:
To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only Geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635.
CONCLUSIONS:
These lines of results suggest that GM in UH is potent 5-HT(1A) receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice. | | Eur J Pharmacol. 2002 May 31;444(3):183-9. | | Geissoschizine methyl ether, an indole alkaloid extracted from Uncariae Ramulus et Uncus, is a potent vasorelaxant of isolated rat aorta.[Pubmed: 12063078] |
METHODS AND RESULTS:
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.
CONCLUSIONS:
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. |
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