21 research outputs found
Relative effects of furosemide and ethacrynic acid on ion transport and energy metabolism in slices of rat kidney-cortex
The effects of furosemide and ethacrynic acid have been studied using slices of rat kidney cortex incubated in a Ringer medium. At concentrations from 0.2–2.0 mM, furosemide had no significant effect on the tissue ATP content or on the metabolism-dependent net movements of intracellular Na + , K + and Ca 2+ . It did, however, induce an increase in the net, outward movement of Cl − ; we suggest that this may have srisen from inhibition of a Cl − accumulating mechanism. In contrast, ethacrynic acid in the same concentration range caused marked reduction of cell respiration and ATP content and virtually total inhibitition of several processes of ion transport (Na + , Cl − and Ca 2+ loss, and K + uptake). Concentrations of furosemide greater than 5 mM caused marked inhibition of energy metabolism and transport of ions, and 10 mM furosemide had quantitatively similar effects to 2 mM ethacrynic acid. Electron micrographs of kidney-cortex slices treated with the diuretics at 2 mM show that the ultrastructure was well maintained in the presence of furosemide but that ethacrynic acid caused severe structural disorganisation and necrosis. The mitochondria were generally in the orthodox configuration in the presence of furosemide, but swollen in ethacrynic acid in accord with the marked effects of 2 mM ethacrynate on mitochondrial energy metabolism. Of the effects we have detected, that of low concentrations of furosemide on Cl − movement appears to be rather specific. Higher concentrations of this agent (5 mM and above), and all concentrations of ethacrynic acid studied (0.1–5.0 mM), have several inhibitory effects which seem to result from primary inhibition of mitochondrial activities and are presumably manifestations of toxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46309/1/210_2004_Article_BF00506264.pd
Ionophore A23187 induced reductions in toad urinary bladder epithelial cell oxidative phosphorylation and viability
The divalent cation ionophore A23187 increased oxygen consumption by isolated epithelial cells from toad urinary bladder, an increase similar to that seen with 2,4-dinitrophenol, a classic uncoupler of mitochondrial oxidative phosphorylation. This respiratory stimulation was not seen in calcium-free incubation media. That this A23187 induced rise in cell oxygen consumption was due to a primary uncoupling action on mitochondrial oxidative phosphorylation rather than secondary to stimulation of cellular transport processes and mediated via increased cellular ADP levels was suggested by the ability of A23187 to release the inhibition of cellular respiration by oligomycin, an inhibitor of the mitochondrial proton ATPase which blocks the stimulation of mitochondrial respiration by ADP. Since active transepithelial ion transport and cellular energy production are closely linked processes, the uncoupling action of A23187 in the presence of extracellular calcium is sufficient to account for an acute decline in active ion transport across epithelia without invoking other calcium-mediated processes. Furthermore, isolated epithelial cells exposed to A23187 for 90 min had greater than 50% loss of viability, as measured by failure of Trypan blue exclusion. The subacute A23187 induced declines in transepithelial transport, therefore, may be secondary to its non-specific effects on cell viability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47447/1/424_2004_Article_BF00658484.pd
ON THE BASIS FOR CELLULAR DAMAGE INDUCED BY ETHACRYNIC ACID IN LIVER SLICES IN VITRO. COMPARISON OF STRUCTURE AND FUNCTION.
OUABAIN-RESISTANT MECHANISM OF VOLUME CONTROL AND ULTRASTRUCTURAL ORGANIZATION OF LIVER SLICES RECOVERING FROM SWELLING IN VITRO.
OBSERVATIONS ON THE REGULATION OF CELL VOLUME AND METABOLIC CONTROL IN VITRO. CHANGES IN THE COMPOSI-TION AND ULTRASTRUCTURE OF LIVER SLICES UNDER CONDI-TIONS OF VARYING METABOLIC AND TRANSPORTING ACTIVITY.
MORPHOLOGICAL STUDIES OF RAT KIDNEY CORTEX SLICES UNDERGOING SWELLING AND ITS REVERSAL: A POSSIBLE BASIS FOR OUABAIN-RESISTANT CONTROL OF CELL VOLUME.
RELATIVE EFFECTS OF FUROSEMIDE AND ETHACRYNIC ACID ON ION TRANSPORT AND ENERGY METABOLISM IN SLICES OF RAT KIDNEY-CORTEX.
ROLE OF CYTOPLASMIC VESICLES IN CELL VOLUME MAINTENANCE.
In Cell Volume Control. Part A: Volume control in isosmotic conditions, Gilles et al., edts., chapter II