Effect of stress on the uptake of 3H-norepinephrine into rat myocardium.

Spontaneously beating atria from rats previously exposed to irregular, signalled footshock were incubated with 3H-norepinephrine. A significant reduction in the uptake and retention of radioactivity was found in the atria from stressed animals compared with unstressed controls. A kinetic study of the uptake process in both the stressed and control groups showed a similar Km value but a significantly different Vmax. It was concluded that the enhanced myocardial sensitivity to catecholamines previously reported can be explained in part, on the basis of an inhibition of neuronal uptake.     

Accumulation of chromium in Chinese hamster V79-cells and nuclei

The bioavailability of carcinogenic compounds plays an important role in the process of oncogenesis. Chromium in its hexavalent oxidation state is classified as carcinogen to humans. Therefore we studied the uptake of chromate(VI) into Chinese hamster V79 cells and nuclei isolated after the incubation of the whole cells with chromate. The chromium content of cells and nuclei was determined by atomic absorption spectroscopy. Chromate is taken up in a concentration dependent manner and accumulates to about 30 fold over the extracellular concentration of 0.1 mmol/1. Incubating whole cells with the same concentration results in an intranuclear concentration of up to 6 mmol/1 after 3 h. The kinetic parameters (K_M = 0.34 mmol/1, V_max = 0.12 fmol per cell and minute) are in the same order of magnitude as previously published data. The consequences of the high intracellular and intranuclear concentrations are discussed in terms of the genotoxic effects.     

Prediction of uptake of methyl mercury by rat erythrocytes using a two-compartment model

 The uptake of methyl mercury (MeHg) by isolated rat erythrocytes was studied at 37°C using MeHg-cysteine (MeHgCySH), MeHg-glutathione (MeHgGSH), MeHg-mercaptalbumin (MeHgMASH) and the mixture of MeHgCySH with MeHgGSH, MeHgCySH with MeHgMASH, MeHgGSH with MeHgMASH at different MeHg concentrations. The measured MeHg concentrations were analyzed according to the Akaike’s information criterion in order to determine the suitable compartment model. After determining a two-compartment model, a model-independent two-compartment model was developed from the kinetics of uptake of MeHg at a concentration of 1 mmol MeHg/l packed erythrocytes using MeHgCySH, MeHgGSH and MeHgMASH, respectively. The developed two-compartment model was validated by predicting the kinetics of uptake of MeHg by rat erythrocytes at different MeHg concentrations and different mixtures of MeHg-complexes. Then, the predicted values were compared with the measured values. The results suggested: 1) MeHg uptake appeared suitable to be described by a two-compartment model, while using MeHgGSH, MeHgMASH, MeHgCySH at lower concentrations and the mixtures of MeHg-complexes; 2) MeHgCySH uptake was slowest among three kinds of MeHg-complexes, although a postulated cysteine-facilitated MeHgCySH transport system might exist in erythrocyte membrane; 3) the mixture of MeHg-complexes might facilitate MeHgCySH uptake; 4) there might be a second MeHg intracellular compartment in rat erythrocytes. Received: 23 February 1995/Accepted: 9 May 1995     

Monoamine uptake inhibitors alter cocaine pharmacokinetics

The time course of change in plasma levels of cocaine and its major metabolite benzoylecognine following 3 mg/kg IV cocaine and the pharmacokinetic interaction between cocaine and several monoamine uptake inhibitors were investigated in conscious rats implanted with arterial and venous cannulae. The IV bolus administration of 3 mg/kg cocaine resulted in plasma levels of 1276±53 ng/ml cocaine at 0.5 min following its injection and the levels then rapidly declined to 768±110 ng/ml by 2 min. Thereafter, the decline of plasma cocaine levels was relatively slow. Plasma benzoylecgonine levels were similar at 0.5 and 2 min following cocaine injection but increased gradually over the next 25 min. Pretreatment with the norepinephrine-selective uptake inhibitors desipramine and nisoxetine, the serotonin-selective uptake inhibitor fluoxetine or the dopamine-selective uptake inhibitor GBR 12909 all enhanced plasma levels of cocaine after a 3 mg/kg IV bolus injection at 0.5, but not at 5 min after injection. The enhancement of plasma cocaine levels by GBR 12909 was of greater magnitude than that produced by desipramine, nisoxetine or fluoxetine. These agents, with the exception of the high dose (10 mg/kg) of GBR 12909, did not significantly alter plasma levels of benzoylecgonine measured at either 0.5 or 5 min following cocaine injection. These results indicate that monoamine uptake inhibitors can alter or interfere with the pharmacokinetics of cocaine and that this interaction is not due to a change in the biotransformation of cocaine. It is suggested that the central monoamine uptake sites serving as rapid distribution sites for cocaine may play a role in this pharmacokinetic interaction.     

Similarity between the effect of experimental congestion of the isolated perfused rat liver and the action of cytochalasin B

Summary Livers of rats were perfused with dextran solutions, containing no red cells. Changes in the dextran concentration due to water shifts between the intra- and extracellular space of the liver were recorded continuously by polarimetric measurement. Cytochalasin B causes an uptake of potassium and water, followed by a release of water and a spontaneously reversible release of potassium, while the liver weight increases. From these effects an uptake of dextran, probably by an endocytotic process, is concluded.     

The effects of isoprenaline and tyramine on the 45calcium uptake,the total calcium content and the contraction force of isolated guinea-pig atria in dependence on different extracellular hydrogen ion concentrations

Summary Isolated, electrically stimulated left guinea-pig atria were incubated at 30° C in a Tyrode solution, the hydrogen ion concentration of which was varied by altering the percentage of the aerating CO₂/O₂-mixture. The increase of the extracellular hydrogen ion concentration from pH 8.0 to pH 7.0 caused a reduction of the ⁴⁵calcium uptake and of the contraction force. The positive inotropic effect and the concomitantly occuring increased ⁴⁵calcium uptake induced by isoprenaline and tyramine were markedly diminished at the lower pH, the response to tyramine being more affected by increased hydrogen ion concentration than that of isoprenaline. This is possibly due to a decrease in noradrenaline available at pH 7.0 for release by tyramine. Isoprenaline and tyramine enhanced the relative specific ⁴⁵calcium activity (RSA) without altering the total tissue calcium content. On the contrary, the increase of the extracellular calcium concentration caused an augmentation of the relative specific ⁴⁵calcium activity and the total tissue calcium content.A preliminary report of this paper was presented at the 12^th meeting of the Deutsche Pharmakologische Gesellschaft: Noack et al., 1971.Supported by the Deutsche Forschungsgemeinschaft.     

Release of endogenous N-acetylaspartylglutamate (NAAG) and uptake of [H]NAAG in Guinea pig cerebellar slices

For the purpose of obtaining chemical information about the physiological role of N-acetylaspartylglutamate (NAAG), the release of endogenous NAAG from and the uptake of [³H]NAAG by Guinea pig cerebellar slices were investigated in comparison with l-aspartate (Asp) and l-glutamate (Glu). Although endogenous NAAG was found to be released spontaneously from the slices as is endogenous Asp and Glu, high-K⁺-induced facilitation of release occurred only for endogenous Asp and Glu in a Ca²⁺-dependent manner, but not for NAAG. It was confirmed that [³H]NAAG itself was taken up in a Na⁺-dependent manner by the slices by two low-affinity processes with small V_max values, and labeled Glu and glutamine were detected as the metabolites of [³H]NAAG in the slices. The [³H]NAAG uptake was slower than that of labeled Glu and was significantly depressed by NAAG, Asp, Glu and d-aspartate, but not affected by γ-aminobutyrate, suggesting that NAAG may share a common uptake carrier with excitatory amino acids. These results suggest that endogenous NAAG may act extracellularly, but the amount of endogenous NAAG released from nerve terminals by presynaptic depolarization may be very small if any, and also that spontaneously liberated NAAG can be inactivated by low-affinity uptake systems, at least, in the Guinea pig cerebellum.     

Platelet serotonin transport after a single ECT

Platelet 5-HT uptake was examined in six depressed patients before and after a single electroconvulsive treatment and compared with six age- and sex-matched controls. The depressed patients had a significantly (P<0.05) lower V _max of platelet 5-HT uptake prior to ECT (22.9±7.6 pm/2×10 platelets) than did control subjects (37.5±9.1 SEM). After a single ECT treatment, the V _max significantly (P<0.05) increased to levels (34.6±10.1) no longer significantly different from control. The results are compared with recent data from depressed patients indicating that low baseline levels of platelet imipramine binding increase after ECT treatment.     

Binding and uptake of putative neurotransmitters in mutant mouse cerebellum and cerebellar reaggregat

γ-Amino butyric acid (GABA) appears to be the inhibitory transmitter of various cerebellar interneurons, while glutamate has been suggested as the excitatory transmitter of granule cells. In this study we have determined the developmental profile from day 2 to day 60 for the Na^a-independent (presumably post-synaptic receptor) binding of [³H]GABA (K_d = 34 nM) and [³H]kainic acid, a glutamate analog (K_d = 53 nM. Both binding activities increase steadily to adult levels with kainic acid achieving this more rapidly. Cerebellar cells (7 day) cultured as reaggregates for 14 days showed an increase in GABA binding and glutamate uptake compared to the starting tissue but did not achieve the levels seen in vivo, while kainic acid binding and GABA uptake remained low. Binding and uptake measurements were performed in neurological mutants. Agranular mutants, weaver, reeler and staggerer demonstrated as expected, marked decreases in total GABA binding and glutamate uptake into synaptosomes, and to a lesser extent GABA uptake. In addition total kainate binding was depressed. In comparison, Purkinje cell degeneration mutants showed only a small decrease in kainic acid binding. These results suggest that kainic acid binding does not identify the post-synaptic glutamate receptor.     

Estimation of individual uptake of trichloroethylene, 1,1,1-trichloroethane and tetrachloroethylene from biological parameters

Summary The results of single exposure studies with exposure to trichloroethylene, TRI, (Monster et al., 1976), to 1,1,1-trichloroethane, MC, (Monster et al., 1979b) and to tetrachloroethylene, PERC, (Monster et al., 1979c) were used to study the precision in estimating the individual uptake from measured biological parameters after exposure. With simple linear and multiple linear regression analysis the individual uptake of TRI, MC and PERC was estimated from the concentrations of solvents and metabolites in biological media (blood, urine, exhaled air) at 2 h and at 20 h after exposure. The best results are obtained by estimation from the concentrations in blood, particularly of the solvents themselves. Including results of simultaneously measured concentrations in exhaled air or urine did not improve the estimate.