Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells.
BACKGROUND
Yokukansan (YKS) is a traditional Japanese medicine consisted of seven medicinal herbs and has been used for treatment of neurosis, insomnia, and behavioral and psychological symptoms of dementia (BPSD) in Japan.


OBJECTIVE
The aim of the present study is to clarify the intrinsic activity of YKS on serotonin (5-HT)1A and 5-HT2A receptors and also to determine the constituent herbs which are responsible for the effect of YKS.


METHODS
The dry powdered extracts of YKS, seven constituent herbs, and YKS-analogues which were produced by eliminating one of the constituent herbs from YKS in the manufacturing process, were used for the evaluation. Competitive binding assays for 5-HT receptors and [(35)S]GTPgammaS binding assays for the evaluation of agonistic/antagonistic activity were performed using Chinese hamster ovary cell membranes stably expressing human recombinant 5-HT1A or 5-HT2A receptors.


RESULTS
YKS (6.25-400 microg/ml) concentration-dependently inhibited the binding of [(3)H]8-OH-DPAT to 5-HT1A receptors. The IC(50) value was estimated to be 61.2 microg/ml. In contrast, YKS failed to inhibit the binding of [(3)H]ketanserin to 5-HT2A receptors. Only Uncaria hook (3.13-50 microg/ml), of the seven constituent herbal extracts, inhibited the [(3)H]8-OH-DPAT binding to 5-HT1A receptors in a concentration-dependent manner, and the IC(50) value was estimated to be 7.42 microg/ml. The extracts of YKS or Uncaria hook increased [(35)S]GTPgammaS binding to 5-HT1A receptors to approximately 50% of that of a full agonist, 5-HT. Both the competitive binding and [(35)S]GTPgammaS binding of YKS to 5-HT1A receptors were remarkably attenuated by eliminating Uncaria hook from YKS, but it was almost unchanged when one of the other constituent herbs was eliminated from YKS.


CONCLUSIONS
These results suggest that YKS has a partial agonistic effect on 5-HT1A receptors, which is mainly attributed to Uncaria hook.
Terawaki
Kiyoshi
K
Tsumura Research Laboratories, Tsumura & Co, 3586 Yoshiwara, Inashiki-gun, Ibaraki 300-1192, Japan.
Ikarashi
Yasushi
Y
Sekiguchi
Kyoji
K
Nakai
Yoichiro
Y
Kase
Yoshio
Y
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018506:Gene Expression Regulation, Plant / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D011994:Recombinant Proteins; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; C524644:Yi-Gan San; D044282:Receptor, Serotonin, 5-HT1A