title: Enhancement of catecholamine release from PC12 cells by the traditional Japanese medicine, rikkunshito.
abstract: BACKGROUND
  Rikkunshito is a traditional Japanese herbal medicine that is used to treat appetite loss associated with cancer and other disorders. The formulation contains various constituents that influence cell signaling, and rikkunshito may accordingly affect human homeostasis through multiple regulatory pathways, including those governed by the endocrine system. We investigated the actions of rikkunshito on catecholamine release from PC12 cells, an adrenal chromaffin cell line.
  
  
  METHODS
  The actions of rikkunshito on PC12 cells were evaluated by measuring intracellular cAMP levels, tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP) mRNA expression levels, and catecholamine levels in the culture medium. The transcriptional activation of VIP gene by rikkunshito was assessed by using a VIP promoter-driven reporter gene assay.
  
  
  RESULTS
  Rikkunshito dose-dependently enhanced forskolin-induced elevations in cAMP in PC12 cells, and also increased the gene expression of TH and VIP. The transcriptional activation of VIP gene by rikkunshito was confirmed. Norepinephrine and dopamine secretion into the culture medium of PC12 cells were also dose-dependently augmented by rikkunshito and/or forskolin, but experiments with a protein kinase C (PKC) activator and a phosphodiesterase inhibitor revealed that the effects of rikkunshito were not simply due to the modulation of PKC or phosphodiesterase activity.
  
  
  CONCLUSIONS
  These findings suggest that rikkunshito enhances the release of catecholamines by a novel mechanism involving cAMP.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Terawaki
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.affiliation: Division of Familial Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ttsukada@ncc.go.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tsukada
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002395:Catecholamines; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C084136:liu-jun-zi-tang; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase