Effects of monensin on ATP levels and cell functions in rat liver and lung in vitro

Abstract

Effects of the proton-alkali cation-exchanging ionophore, monensin, on aspects of cellular metabolism and ionic exchanges have been studied in rat tissues in vitro. Incubation of liver slices at 38 degrees C with 0.1 microM monensin induced time-dependent vesiculation, initially in the Golgi region, reduction of ATP content and of protein synthesis. At 1 microM, monensin also reduced net, active movements of K+, Na+, Cl- and water in liver slices and inhibited state 3 respiration in isolated mitochondria. The respiratory inhibitor, amytal, similarly reduced ATP content and protein synthesis at concentrations lower than those inhibiting ion transport in slices. Low concentrations of monensin (0.1-1.0 microM) had similar effects on ATP and ion transport in slices of adult lung. By contrast, late-fetal liver and lung were much less sensitive to monensin; in these tissues, glycolysis sustained substantial levels of ATP. Monensin also induced vesiculation of the Golgi apparatus in fetal lung cells. It is concluded that by lowering ATP levels, monensin can markedly alter various metabolic activities in those cells which depend primarily on oxidative phosphorylation for their metabolic energy.

Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function

“…1b ). None of these treatments affected the brightness of host mitochondria, which is not surprising since we are using concentrations at least 50 times below those used to elicit changes in mammalian host mitochondria 13 29 31 .…”

“…As a Na + /H + exchanging ionophore 27 , monensin is expected to disrupt ionic gradients across cellular membranes 28 . In various rat tissues including testis, liver, and lung, monensin was demonstrated to interfere with the proper shuttling of protons across the IMM leading to a loss in mitochondrial membrane potential as well as interruption of the electron transport chain, oxidative phosphorylation, and ATP production 29 30 . In murine fibroblasts, monensin-induced toxicity was shown to create an ionic imbalance that greatly affected the morphology of mitochondria 14 31 .…”

Mobile ionophores are a novel class of P‐glycoprotein inhibitors

“…Recent studies using carboxylic ionophores such as monensin and nigericin have indicated that these agents can modulate anthracycline toxicity apparently by causing an enhancement of anthracycline accumulation (Sehested et al, 1988;Klohs and Steinkampf, 1988). It has also been noticed that the cytotoxic action of drugs such as monensin (Mariani et al, 1989) and nigericin (Rotin et al, 1987) may be due to a decrease in the cellular ATP level.…”

Studies on Monensin Toxicity in Goats

“…Since the primary metabolic pathways for monensin appear to be 0-demethylation and hydroxylation (DONOHO et al, 1978), the reactions catalyzed by microscomal monooxygenases, it is likely that monensin at a non-toxic dosage level may have induced the activity of the monooxygenases. O n the other hand, decreased activity of the microsomal enzymes caused by 55 pprn monensin may be attributed to the reduction of ATP, and consequently protein synthesis, by the highest dose of monensin in liver cells due, at least partly, to its effect on mitochondria (MARIANI et al, 1989). Monensin is believed to cause movement of extracellular calcium into the cell (LANGSTON et al, 1985;BOURQUE et al, 1986).…”