scholarly journals Cyclosporin A and verapamil have different effects on energy metabolism in multidrug-resistant tumour cells

1990 ◽  
Vol 62 (1) ◽  
pp. 85-88 ◽  
Author(s):  
HJ Broxterman ◽  
HM Pinedo ◽  
GJ Schuurhuis ◽  
J Lankelma
Keyword(s):  
Energy Metabolism ◽  
Cyclosporin A ◽  
Multidrug Resistant ◽  
Tumour Cells

Identification of the synthetic surfactant nonylphenol ethoxylate: a P-glycoprotein substrate in human urine

1998 ◽  
Vol 274 (6) ◽  
pp. F1127-F1139 ◽  
Author(s):  
Jeffrey H. M. Charuk ◽  
Arthur A. Grey ◽  
Reinhart A. F. Reithmeier
Keyword(s):  
Cyclosporin A ◽  
Drug Transport ◽  
Mdck Cells ◽  
Chinese Hamster ◽  
Multidrug Resistant ◽  
The Body ◽  
Transepithelial Transport ◽  
Synthetic Surfactant ◽  
Nonylphenol Ethoxylate ◽  
P Glycoprotein

P-glycoprotein (Mdr1p) is an ATP-dependent drug efflux pump that is overexpressed in multidrug-resistant cells and some cancers. Mdr1p is also expressed in normal tissues like the kidney, where it can mediate transepithelial drug transport. A human urinary compound that reverses multidrug resistance and blocks [3H]azidopine photolabeling of P-glycoprotein was purified to homogeneity and identified by 1H-NMR and mass spectrometry as the synthetic surfactant nonylphenol ethoxylate (NPE). Multidrug-resistant Chinese hamster ovary (CHO) C5 cells accumulated less [3H]NPE than parental drug-sensitive Aux-B1 cells, and Mdr1p substrates, verapamil and cyclosporin A, increased this surfactant’s accumulation in C5 cells. NPE blocked the net transepithelial transport (basolateral to apical) of [3H]cyclosporin A in epithelia formed by Madin-Darby canine kidney (MDCK) cells. Net transepithelial transport (basal to apical) of [3H]NPE was demonstrated in MDCK cells and was inhibited by cyclosporin A. These findings show NPE is a Mdr1p substrate excreted into urine by kidney P-glycoprotein. NPE is a widely used surfactant and a known hormone disrupter that is readily absorbed orally or topically. The current findings indicate the function of kidney Mdr1p may be to eliminate exogenous compounds from the body.

scholarly journals Comparison of the Effects of Cyclosporin a on the Metabolism of Perfused Rat Brain Slices during Normoxia and Hypoxia

2002 ◽  
Vol 22 (3) ◽  
pp. 342-352 ◽  
Author(s):  
Natalie Serkova ◽  
Paul Donohoe ◽  
Sven Gottschalk ◽  
Carsten Hainz ◽  
Claus U. Niemann ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cyclosporin A ◽  
Rat Brain ◽  
Ex Vivo ◽  
Brain Slices ◽  
High Energy ◽  
Metabolic Effects ◽  
Resonance Spectroscopy ◽  
Buffer Solution ◽  
Mitochondrial Energy Metabolism

The authors evaluated and compared the metabolic effects of cyclosporin A in the rat brain during normoxia and hypoxia/reperfusion. Ex vivo31P magnetic resonance spectroscopy experiments based on perfused rat brain slices showed that under normoxic conditions, 500 μg/L cyclosporin A significantly reduced mitochondrial energy metabolism (nucleotide triphosphate, 83 ± 9% of controls; phosphocreatine, 69 ± 9%) by inhibition of the Krebs cycle (glutamate, 77 ± 5%) and oxidative phosphorylation (NAD+, 65 ± 14%) associated with an increased generation of reactive oxygen species (285 ± 78% of control). However, the same cyclosporin A concentration (500 μg/L) was found to be the most efficient concentration to inhibit the hypoxia-induced mitochondrial release of Ca2+ in primary rat hippocampal cells with cytosolic Ca2+ concentrations not significantly different from normoxic controls. Addition of 500 μg/L cyclosporin A to the perfusion medium protected high-energy phosphate metabolism (nucleotide triphosphate, 11 ± 15% of control vs. 35 ± 9% with 500 μg/L cyclosporin A) and the intracellular pH (6.2 ± 0.1 control vs. 6.6 ± 0.1 with cyclosporin A) in rat brain slices during 30 minutes of hypoxia. Results indicate that cyclosporin A simultaneously decreases and protects cell glucose and energy metabolism. Whether the overall effect was a reduction or protection of cell energy metabolism depended on the concentrations of both oxygen and cyclosporin A in the buffer solution.

scholarly journals Reversal activity of cyclosporin A and its metabolites M1, M17 and M21 in multidrug-resistant cells

1997 ◽  
Vol 71 (5) ◽  
pp. 900-906 ◽  
Author(s):  
Giuseppe Toffoli ◽  
Giuseppe Corona ◽  
Roberto Sorio ◽  
Antonella Bertola ◽  
Mauro Boiocchi
Keyword(s):  
Cyclosporin A ◽  
Multidrug Resistant ◽  
Resistant Cells

scholarly journals Selective modulation of vinblastine sensitivity by 1,9-dideoxyforskolin and related diterpenes in multidrug resistant tumour cells

1993 ◽  
Vol 67 (3) ◽  
pp. 471-479 ◽  
Author(s):  
DR Shalinsky ◽  
DD Heath ◽  
AP Jekunen ◽  
JE Alcaraz ◽  
SB Howell
Keyword(s):  
Multidrug Resistant ◽  
Tumour Cells ◽  
Selective Modulation
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