Abstract
We have tested whether toxicity and uptake of ouabain are linked phenomena in isolated guinea-pig heart. We perfused toxic dose of either ouabain, dihydroouabain (hydrophilic cardiac steroids), ouabagenin or digitoxin (hydrophobic steroids) in conditions of endocytosis inhibited. We used two schemes of inhibition of endocytosis. First, we cooled the heart at 0-4 degrees C and exposed it 60 min to either 1 X 10(-6) M ouabain or 3 X 10(-7)M digitoxin. Upon rewarming, the heart exposed to ouabain relaxed with a shorter time constant than those exposed to digitoxin. Second, we perfused four receptor mediated endocytosis (RME) inhibitors at the same time that the cardiac glycosides. RME inhibitors significantly delayed the cardiac arrest caused by ouabain and dihydroouabain but they did not modify the toxicity of 3 X 10(-7)M digitoxin or 5 X 10(-6)M ouabagenin. None of RME inhibitors modified the toxicity of 0.5 mM K+ or zero Na+ saline solution. We suggest that the protection against ouabain toxicity brought by endocytosis inhibition, is related to the Na-pump recycling. We infer that besides the sarcolemmal exposed Na-pumps, the intracellular Na-pumps pool may be of importance for the pharmacological effects of digitalis steroids.
References
Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H HallaqA Leaf
Dec 1, 1986·The Journal of Physiology·M R BoyettA J Levi
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R FuchsI Mellman
Oct 1, 1988·The American Journal of Physiology·H Núñez-DuránL Bárcenas-Ruiz
Jan 1, 1974·Annals of the New York Academy of Sciences·A Yoda
Sep 1, 1980·Cardiovascular Research·D Noble
Jan 1, 1982·Journal of Cellular Physiology·J S CookC Shaffer
Jan 1, 1982·Quarterly Journal of Experimental Physiology : an International Journal of the Physiological Society·J F Lamb, P Ogden
Jan 1, 1984·The Biochemical Journal·R T DeanC R Roberts
Feb 1, 1980·Circulation Research·K R Levin, E Page
Aug 1, 1993·Cardiovascular Research·M A VosH J Wellens
Apr 1, 1993·British Journal of Pharmacology·S J McGarry, A J Williams
Apr 22, 1993·European Journal of Pharmacology·H R LuF De Clerck
Nov 15, 1985·Physical Review. D·M D KovarikR Koniuk
Jan 29, 2010·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Giuseppe RengoDario Leosco
Citations
Jan 7, 2004·Life Sciences·Harol Núñez-Durán, Paola Fernández
Jul 6, 2007·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Wilhelm Schoner, Georgios Scheiner-Bobis
Apr 29, 2010·British Journal of Pharmacology·M NesherD Lichtstein
Feb 20, 1999·Cytokine·A M ScarozzaK Wicher
May 15, 2007·American Journal of Physiology. Cell Physiology·Wilhelm Schoner, Georgios Scheiner-Bobis
Jan 20, 2006·Journal of Medicinal Chemistry·Joseph DeutschDavid Lichtstein