Effects of Geissoschizine Methyl Ether, an Indole Alkaloid in Uncaria Hook, a Constituent of Yokukansan, on Human Recombinant Serotonin7 Receptor

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.