Literature DB >> 22968712

Effects of geissoschizine methyl ether, an indole alkaloid in Uncaria hook, a constituent of yokukansan, on human recombinant serotonin 7 receptor.

Toshiyuki Ueki1, Akinori Nishi, Sachiko Imamura, Hitomi Kanno, Kazushige Mizoguchi, Kyoji Sekiguchi, Yasushi Ikarashi, Yoshio Kase.   

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.

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Year:  2012        PMID： 22968712     DOI： 10.1007/s10571-012-9878-3

Source DB:  PubMed          Journal:  Cell Mol Neurobiol        ISSN： 0272-4340            Impact factor:   5.046


  31 in total

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