Nordihydroguaiaretic acid depletes ATP and inhibits a swelling-activated, ATP-sensitive taurine channel

The American Journal of Physiology
N Ballatori, W Wang

Abstract

The mechanism by which nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, prevents swelling-activated organic osmolyte efflux was examined in the human hepatoma cell line Hep G2. When swollen in hypotonic medium, Hep G2 cell exhibited a regulatory volume decrease that was associated with the release of intracellular taurine, an amino acid found at a concentrations of 22.0 +/- 2.5 nmol/mg protein (approximately 5 mM) in these cells. Rate coefficients for swelling-activated [3H]taurine uptake and efflux were unaffected when extracellular taurine was increased from 0.1 to 25 mM, indicating that taurine is released via a channel. Taurine efflux was rapidly activated after cell swelling and immediately inactivated when cells were returned to normal size by restoration of isotonicity. Swelling-activated taurine efflux was not altered by replacement of extracellular Na+ with choline+ or K+ but was inhibited when cellular ATP levels were decreased with a variety of chemical agents, consistent with an ATP-regulated channel previously described in other cell types. NDGA inhibited swelling-activated [3H]taurine efflux in Hep G2 cells at concentrations of 50-150 microM; however, these same concentrations of NDGA also lowered cell ...Continue Reading

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Citations

Apr 21, 2001·The Journal of Physiology·R WondergemK E Ferslew
Aug 1, 2014·American Journal of Physiology. Cell Physiology·Hercules A da Silva-SouzaEliana Scemes
Oct 24, 2019·Current Cancer Drug Targets·Geraldine Sandana Mala JohnSuresh Kumar Rayala
Aug 4, 1998·The American Journal of Physiology·Y LiuY Okada
Jul 8, 2015·Expert Opinion on Drug Metabolism & Toxicology·Carlemi CalitzSias Hamman
Oct 24, 2006·Medical Hypotheses·Anthony G Payne

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