Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in hepatocytes.
The effect of nordihydroguaiaretic acid (NDGA) on Ca(2+) signaling in human hepatoma cells (HA22/VGH) has been investigated. NDGA (5-50 microM) increased [Ca(2+)](i) concentration-dependently. The [Ca(2+)](i) increase comprised an initial rise and an elevated phase over a time period of 4 min. Removal of extracellular Ca(2+) reduced 10-50 microM NDGA induced [Ca(2+)](i) signals by 45+/-5%. Consistently, the 50 microM NDGA-induced [Ca(2+)](i) increase in Ca(2+)-containing medium was reduced by 41+/-2% by 10 microM of La(3+), nifedipine or verapamil. In Ca(2+)-free medium, pretreatment with 20 microM NDGA for 6 min abolished the [Ca(2+)](i) increase induced by the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM). Conversely, 20 microM NDGA failed to increase [Ca(2+)](i) after 1 microM thapsigargin had depleted the endoplasmic reticulum Ca(2+) store. Inhibition of phospholipase C with 2 microM U73122 had little effect on 20 microM NDGA-induced Ca(2+) release. Several other lipoxygenase inhibitors had no effect on basal [Ca(2+)](i). Together, the data suggest that NDGA increased [Ca(2+)](i) in hepatocytes in a lipoxygenase-independent manner, by releasing Ca(2+) from the endoplasmic reticulum and causing Ca(2+) influx.
Department of Medicine, Kaohsiung Veterans General Hospital, 386 Ta Chung 1st Road, Kaohsiung 813, Taiwan.
Jin-Shiung
JS
Cheng
Chung-Ren
CR
Jan
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004963:Estrenes / Q000494:pharmacology; D016257:Fura-2 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000633:toxicity*; D009637:Masoprocol / Q000633:toxicity*; D009543:Nifedipine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D004963:Estrenes; D016859:Lipoxygenase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019284:Thapsigargin; D007811:Lanthanum; D009637:Masoprocol; D006632:Histamine; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2