title: Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells.
abstract: What's known on the subject? And what does the study add? Schisandra chinensis extract (SCE) has been known to have relaxative effects on penile smooth muscle. A recent study showed that SCE could enhance slidenafil citrate-induced relaxation of penile corpus cavernosum. The current study investigated the mechanism of action of SCE and its constituents on corporal smooth muscle cells. And this study shows that SCE induced relaxation of CSM primarily through an endothelium independent pathway and the relaxation effects of SCE on corporal smooth muscle are, in part, due to the activation of K(+) channels and inhibition of TRPC6 channels, resulting in decreased [Ca(2+)].
  
  
  OBJECTIVE
  • To evaluate the relaxant effects of Schisandra chinensis extract (SCE) on corporal tissue in the penis and to investigate the mechanism of action of SCE and its constituents on corporal smooth muscle (CSM) cells.
  
  
  METHODS
  • The fruit of SC was collected and extracted with ethanol. Six SC lignans (schisandrol A, schisandrol B, schisandrin A, schisandrin B, gomisin N, and schisandrin C) were isolated and purified, and the chemical structures were confirmed by (1)H-nuclear magnetic resonance (NMR) and (13)C-NMR data. • Isolated rabbit CSM strips were mounted in an organ-bath system, and the effects of SCE were evaluated. • To estimate the intracellular Ca(2+) level ([Ca(2+)](i)), we used a Fura-2 fluorescent technique, and a conventional whole-cell patch-clamp technique was used to measure the calcium-sensitive K(+) channels (K(Ca)), inward rectifier K(+) channels (K(IR)), and canonical transient receptor potential cation channel 6 (TRPC6) currents.
  
  
  RESULTS
  • SCE induced concentration-dependent relaxation in contracted CSM tissue, and the removal of the endothelium did not significantly affect their relaxation potencies. • In CSM cells, extracellular application of SCE significantly increased whole-cell K(Ca) currents (117.4%) and K(IR) currents (110.0%). These effects were completely abolished by charybdotoxin or BaCl(2). • In contrast, carbachol-induced TRPC6 channel activity was significantly inhibited (87.3%) by SCE in green fluorescent protein-TRPC6 pcDNA transfected HEK 293 cells. [Ca(2+)](i) measurements showed that SCE effectively reduced basal [Ca(2+)](i) in both cell lines (CSM cells and A7r5 cells) and the [Arg8]-vasopressin (AVP)-induced [Ca(2+)](i) increase in A7r5 cells. • Among the six SC lignans, schisandrin A and schisandrin B most effectively attenuated the AVP-induced [Ca(2+)](i) increase.
  
  
  CONCLUSIONS
  • SCE induced relaxation of CSM that occurred primarily via an endothelium-independent pathway. • The relaxation effects of SCE on CSM were, in part, due to the activation of K(+) channels and inhibition of TRPC6 channels, resulting in decreased [Ca(2+)](i).
authors.affiliation: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Deok Hyun
authors.initials: DH
authors.lastname: Han
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Kim
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Ko
authors.forename: Mee Ree
authors.initials: MR
authors.lastname: Chae
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D005638:Fruit / Q000737:chemistry*; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010413:Penis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D011817:Rabbits; D032141:Schisandra / Q000737:chemistry*; D050052:TRPC Cation Channels / Q000187:drug effects
chemical_list: D005456:Fluorescent Dyes; D010936:Plant Extracts; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D050052:TRPC Cation Channels; D016257:Fura-2