title: Effect of gingerol on colonic motility via inhibition of calcium channel currents in rats.
abstract: OBJECTIVE
  To investigate the effect of gingerol on colonic motility and the action of L-type calcium channel currents in this process.
  
  
  METHODS
  The distal colon was cut along the mesenteric border and cleaned with Ca(2+)-free physiological saline solution. Muscle strips were removed and placed in Ca(2+)-free physiological saline solution, which was oxygenated continuously. Longitudinal smooth muscle samples were prepared by cutting along the muscle strips and were then placed in a chamber. Mechanical contractile activities of isolated colonic segments in rats were recorded by a 4-channel physiograph. Colon smooth muscle cells were dissociated by enzymatic digestion. L-type calcium currents were recorded using the conventional whole-cell patch-clamp technique.
  
  
  RESULTS
  Gingerol inhibited the spontaneous contraction of colonic longitudinal smooth muscle in a dose-dependent manner with inhibition percentages of 13.3% ± 4.1%, 43.4% ± 3.9%, 78.2% ± 3.6% and 80.5% ± 4.5% at 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L, respectively (P < 0.01). Nifedipine, an L-type calcium channel blocker, diminished the inhibition of colonic motility by gingerol. Gingerol inhibited L-type calcium channel currents in colonic longitudinal myocytes of rats. At a 75 μmol/L concentration of gingerol, the percentage of gingerol-induced inhibition was diminished by nifedipine from 77.1% ± 4.2% to 42.6% ± 3.6% (P < 0.01). Gingerol suppressed IBa in a dose-dependent manner, and the inhibition rates were 22.7% ± 2.38%, 35.77% ± 3.14%, 49.78% ± 3.48% and 53.78% ± 4.16% of control at 0 mV, respectively, at concentrations of 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L (P < 0.01). The steady-state activation curve was shifted to the right by treatment with gingerol. The value of half activation was -14.23 ± 1.12 mV in the control group and -10.56 ± 1.04 mV in the 75 μmol/L group (P < 0.05) with slope factors, Ks, of 7.16 ± 0.84 and 7.02 ± 0.93 (P < 0.05) in the control and 75 μmol/L groups, respectively. However, the steady-state inactivation curve was not changed, with a half-inactivation voltage, 0.5 V, of -27.43 ± 1.26 mV in the control group and -26.56 ± 1.53 mV in the 75 μmol/L gingerol group (P > 0.05), and a slope factor, K, of 13.24 ± 1.62 in the control group and 13.45 ± 1.68 (P > 0.05) in the 75 μmol/L gingerol group.
  
  
  CONCLUSIONS
  Gingerol inhibits colonic motility by preventing Ca(2+) influx through L-type calcium channels.
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Zheng-Xu
authors.initials: ZX
authors.lastname: Cai
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Tang
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Feng-Yun
authors.initials: FY
authors.lastname: Wang
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Duan
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Li
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Qiu
authors.affiliation: Zhi-Jun Duan, Yu-Chun Li, Juan-Juan Qiu, Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors.forename: Hui-Shu
authors.initials: HS
authors.lastname: Guo
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002396:Catechols / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002396:Catechols; D005233:Fatty Alcohols; C007845:gingerol
keywords: Colonic motility; Gingerol; L-type calcium channel current; Longitudinal smooth muscle myocytes; Spontaneous contraction