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Forschungsdatenbank PMU-SQQUID

Hydroperoxide metabolism in rat liver. K+ channel activation, cell volume changes and eicosanoid formation.
Hallbrucker, C; Ritter, M; Lang, F; Gerok, W; Häussinger, D;
Eur J Biochem. 1993; 211(3): 449-458.
Originalarbeiten (Zeitschrift)


Ritter Markus


Addition of t-butylhydroperoxide (0.2 mM) to isolated perfused rat liver ted to a net K+ release of 7.2 +/- 0.2 mumol/g within 8 min and a net K+ reuptake of 6.6 +/- 0.4 mumol g following withdrawal of the hydroperoxide, in line with earlier findings by Sies et al. [Sies, H., Gerstenecker, C., Summer, K. H., Menzel, H. *** Flohe, R. (1974) in Glutathione (Flohe, L., Benohr, C., Sies, H., Waller, H. D., eds) pp. 261-276, G. Thieme Publ. Stuttgart]. Net K+ release roughly paralleled the amount of GSSG released from the liver under the influence of the hydroperoxide. The t-butylhydroperoxide-induced K+ efflux was inhibited by approximately 70% in the presence of Ba2+ (1 mM), by 30% in Ca2+ free perfusions and was decreased by 50 - 60% when the intracellular Ca2+ stores were simultaneously depleted by repeated additions of phenylephrine. t-Butylhydroperoxide-induced K+ efflux was accompanied by a decrease of the intracellular water space by 58 +/- 14 mul/g (n = 4), corresponding to a 10% cell shrinkage. The effect of t-butylhydroperoxide on cell volume was inhibited by 70 - 80% in the presence of Ba2+. In isolated rat hepatocytes treatment with t-butylhydroperoxide led to a slight hyperpolarization of the membrane at concentrations of 100 nM, but marked hyperpolarization occurred at t-butylhydroperoxide concentrations above 10 muM. t-Butylhydroperoxide (0.2 mM) transiently increased the portal-perfusion pressure by 3.3 +/- 0.6 cm H2O (n = 18), due to a slight stimulation of prostaglandin-D2 release under the influence of the hydroperoxide. In the presence of Ba 2+ (1 mM), t-butylhydroperoxide increased the perfusion pressure by 12.7 +/- 1.2 cm H2O (n = 9) and produced an approximately tenfold increase of prostaglandin-D2 and thromboxane-B2 release. Under these conditions, glucose output from the liver rose from 0.9 +/- 0.03 to 2.9 +/- 0.7 mumol . g-1 . min-1 (n = 4) with a time course roughly resembling that of portal-pressure increase and prostaglandin-D2 overflow. These effects were largely abolished in the presence of ibuprofen or the thromboxane-receptor-antagonist BM 13.177. The t-butylhydroperoxide effects on perfusion pressure, glucose and eicosanoid output were also enhanced in the presence of insulin or during hypotonic exposure; i.e. conditions known to swell hepatocytes, but not during hyperosmotic exposure. The data suggest that t-butylhydroperoxide induces liver-cell shrinkage and hyperpolarization of the plasma membrane due to activation of Ba2+-sensitive K+ channels. Ca2+ is apparently required for the t-butylbydroperoxide-induced K+ channel activation, and K+ efflux may be related to cellular thiol oxidation. t-Butylhydroperoxide stimulates the formation of cyclooxygenase products. The data show that hydroperoxide effects on hepatic metabolism are more complex than previously thought; both, cell shrinkage and eicosanoid formation under the influence of t-butylhydroperoxide may contribute to its known glycogenolytic effect.

Useful keywords (using NLM MeSH Indexing)





Liver/drug effects*



Membrane Potentials/drug effects

Osmolar Concentration




Potassium Channels/drug effects*

Potassium Channels/physiology


Prostaglandin D2/biosynthesis


Rats, Wistar

Thromboxane B2/biosynthesis