Novel action of lignans isolated from Hernandia nymphaeifolia on Ca(2+) signaling in renal tubular cells.
The effect of five lignans, epi-aschantin, epi-magnolin, epi-yangambin, deoxypodophyllotoxin and yatein, isolated from Hernandia nymphaeifolia on Ca(2+) signaling in Madin-Darby canine kidney cells was examined using fura-2 as a Ca(2+) indicator. These lignans at concentrations between 10 and 100 microM increased [Ca(2+)](i) in a concentration-dependent manner. Removal of extracellular Ca(2+) abolished the Ca(2+) signals evoked by 50 microM of the lignans. La(3+)(50 microM) abolished the Ca(2+) signals induced by 100 microM of epi-aschantin, epi-magnolin and epi-yangambin, and 20 microM deoxypodophyllotoxin, but inhibited by 60% 50 microM yatein-induced responses. All five lignans (50-100 microM) inhibited by 42-65% thapsigargin-induced capacitative Ca(2+) entry, and inhibited by 23-61% thapsigargin-induced intracellular Ca(2+) release. Epi-yangambin (100 microM), epi-magnolin (100 microM), and epi-aschantin (100 microM) inhibited by 8-38% 10 microM ATP-induced Ca(2+) release. Trypan blue exclusion revealed that incubation with deoxypodophyllotoxin or yatein (but not the other lignans) decreased cell viability in a concentration-dependent manner. Together, the results suggest that, in renal tubular cells, these lignans exert multiple actions on Ca(2+) signaling. They caused Ca(2+) influx but reduced thapsigargin-induced capacitative Ca(2+) entry and also thapsigargin- and ATP-induced Ca(2+) release. Additionally, deoxypodophyllotoxin and yatein may be cytotoxic.
Chao
Yu-Ying
YY
Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chen
Ih-Sheng
IS
Yeh
Jwu-Lai
JL
Chen
Jih-Jung
JJ
Ko
Ying-Chin
YC
Cheng
Jin-Shiung
JS
Liu
Chun-Peng
CP
Lo
Yuk-Keung
YK
Su
Warren
W
Chou
Kang-Ju
KJ
Chen
Wei-Chung
WC
Jan
Chung-Ren
CR
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D005110:Extracellular Space; D005456:Fluorescent Dyes; D016257:Fura-2; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D019684:Magnoliopsida / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D005456:Fluorescent Dyes; D017705:Lignans; D010936:Plant Extracts; D019284:Thapsigargin; D007811:Lanthanum; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2