[Effect of corticosteroids on the glucose as well as sodium- and potassium-ion levels in the rabbit aqueous humor].
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The erythrocyte concentrations and the transmembrane fluxes of sodium and potassium were investigated in normal men and also in twenty normal women during the two stages of the menstrual cycle. Half of them were taking the contraceptive pill and the other half were not. In women with a normal menstrual cycle, the erythrocyte sodium concentration (Naic) and the ouabain-insensitive total potassium efflux were lower in the luteal than in the follicular phase. Intracellular potassium concentration (Kic), ouabain-sensitive 86rubidium-uptake and the furosemide-sensitive Na+ and K+ efflux did not differ significantly between the two periods of the cycle. No cycle-related variation in Naic or Kic was observed in women using the contraceptive pill. In these women, however, the ouabain-sensitive 86rubidium-uptake was increased in the second part of the menstrual cycle. Compared to men, the intra-erythrocyte sodium concentration was lower in women during the second stage of the menstrual cycle. These two groups were similar for Na+, K+-ATPase pump activity estimated from the ouabain-sensitive 86rubidium-uptake and for the furosemide-sensitive sodium and potassium efflux. Women in the first stage of the menstrual cycle had intra-erythrocyte sodium concentration similar to men, but their furosemide-sensitive sodium efflux was lower. No significant difference was observed in the intraerythrocyte potassium concentration and transmembrane fluxes of potassium in men and women in either stage of the menstrual cycle. We therefore conclude from this study that one should take into account sex-related variability when studying cationic fluxes and concentrations in red blood cells of men and women.
A calcium-dependent cyclic nucleotide phosphodiesterase from rat cerebrum was, in the absence of activator protein, inhibited by various monovalent cations. The inhibition was rapid, readily reversible, and concentration-dependent, with 100 mM cesium, rubidium, or potassium ion inhibiting essentially all basal enzyme activity, while 100 mM sodium or lithium ions produced only moderate inhibition. The potency of the cations in inhibiting the enzyme was Cs greater than or equal to Rb greater than K greater than Na greater than or equal to Li. Potassium ions increased the apparent Km for cyclic GMP and cyclic AMP by 3- and 5-fold, respectively. At 100 mM, the monovalent cations inhibited enzyme activated by the calcium-dependent activator by only 15 to 30%, while at 55 mM no inhibition pertained. Potassium and sodium ions at 55 mM had no effect on the calcium-independent phosphodiesterase from rat cerebrum. The results indicate that at normal intracellular concentrations of potassium ions the activity of the calcium-dependent phosphodiesterase is virtually completely dependent on the presence of calcium plus activator protein.
When freshly isolated rabbit lenses were co-cultured with iris-ciliary body (IC), the protein synthetic activity of these lenses decreased significantly. The inhibitory effect is temporal as longer incubation showed greater inhibition. it was also found that the presence of IC in the culture medium increases the sodium ion levels in the lenses and causes some decrease in the potassium ion levels. Both the protein synthetic activity and cation levels of the lenses cocultured with IC are at least partially reversible. It seems that the IC-derived factor(s) has a molecular weight of more than 1 kDa. It is not clear from these experiments whether the altered cation balance is responsible for the inhibition of the protein synthesis.
Various reagents used in the chemical modification of amino- and carboxy-groups of proteins, and of carbohydrates of glycoproteins and glycolipids, inhibit respiration in ascites tumor cells concomitant with release of potassium ion from those cells. The respiratory activity of washed ascites tumor cells is increased by exogenous addition of potassium ion. The lowered respiratory control index as well as oxidative phosphorylation of aged mitochondria are restored upon increasing the potassium concentration of the incubation mixture in the presence of respiratory substrates. The data suggest that the potassium ion level of cells is changed by modifying physicochemical properties of membrane components and that cellular energy metabolism is regulated by intracellular potassium ion concentration.
This study was of a series of the evaluation of Hachimi-Jio-Gan (Rehmannia Eight Formula, pa-wei-ti-huang-wan or Bawei dihuang wan) to the various cataracts. In this study, the drug was evaluated for its therapeutic efficacy to mouse hereditary cataract from the delay effect of cataract appearance age and the suppression rates of variation of some biochemical parameters. The dose of 200 mg of Hachimi-Jio-Gan/day/100 g of mouse body weight significantly delayed the cataract appearance age by 4 days as compared to that of non-treated group. We estimated that the delay effect of 4 days in mouse may be corresponded to 13.9 years, when it was converted into the case of human. This drug also suppressed variation of sodium and potassium ions level in the lens with cataractogenesis. Furthermore, the drug dramatically reactivated the sodium-potassium ATPase activity damaged with the cataract formation, and also had a slight action of reducing agent. From these facts, we presumed that the drug may have a prophylactic efficacy to the cataract caused by the inhibition of sodium-potassium ATPase activity and also the oxidation of lens protein.
Direct measurements of electrical potential and input resistance were performed on the syncytial membrane facing maternal blood. The potentials varied according to the external potassium ion levels and, to a lesser extent, with sodium ion concentrations. Ouabain provoked a rapid and consistent depolarization which indicates an electrogenic component. Amiloride slightly hyperpolarized the membrane, confirming the predominant role of potassium ions in the control of the diffusional component of the membrane potential. The electrical potential revealed in this study might play a part in the maternofetal transport of ions.
The Nakano mouse is a hereditary cataract model whose most characteristic change is a deficiency in lens Na+,K(+)-ATPase. Consequently, there is a change in lenticular sodium and potassium ion levels just before cataract formation. The amounts of calcium ion also change suddenly in the lens, with accumulated levels higher than any other type of cataract. Other biochemical changes coincide with the development of lens opacity, including decreases in the levels of reduced glutathione, ATP, biosynthetic activity of proteoglycans in epithelial cells, and the permeability of gap junction channels in fiber cells. The decrease in the activity of Na+,K(+)-ATPase results in changes in a number of key metabolic parameters, resulting in the eventual opacification of the Nakano mouse lens at approximately 30 days of age.
The functional state of the gastric mucosa in dogs after 12.7 Gy abdominal X-ray irradiation was examined. During the first 7 days after irradiation, hypochylia, decrease of proteolytic activity and the H+ (hydrogen-ion) production in the gastric juice was observed. The gastric mucosal cells of rats were examined after the irradiation with 12 Gy to find out the reason for hypochylia. Possibly the reduction of the number of the gastric mucosal cells and their protein content one day after the irradiation, as well as functional disorders of the outer membrane--expressed by the decrease of the intracellular K+ (potassium-ion) level and the ATPase and 5'-nucleotidase activity--may be the reasons for the hypochylia after irradiation.
Potassium fluxes, ouabain binding, and Na+ and K+ intracellular concentrations were determined for cultures of growing normal, density-inhibited and Rous sarcoma virus-transformed chicken embryo fibroblasts. No significant differences in K+ influx or ouabain binding were detected between growing normal cells and Rous sarcoma virus-transformed cells; however, ouabain binding and ouabain-sensitive K+ influx were 1.5- to 1.8-fold lower in density-inhibited cells. Thus, potassium influx in this system can be classified as a growth-related, but not transformation-specific change. As determined by both flame photometry and radioisotopic (42K) equilibration, growing normal and density-inhibited cells had similar potassium contents, whereas transformed cells exhibited 1.4-fold higher potassium levels. Sodium ion levels, as measured by flame photometry, were also 2- to 4.5-fold higher in transformed than normal or density-inhibited cells. Complementary studies of potassium efflux showed a 1.3- to 1.5-fold higher rate (based on the percentage of pool exiting the cell) in growing normal versus density-inhibited or transformed fibroblasts. Because of the larger potassium pool in transformed cells, efflux based on absolute number of potassium ions is similar in normal and transformed chicken embryo fibroblasts.
It has been reported that Escherichia coli is able to grow in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) when ATP is produced by glycolysis (N. Kinoshita et al., J. Bacteriol. 160:1074-1077, 1984). We investigated the effect of CCCP on the osmotic adaptation of E. coli growing with glucose. When E. coli growing in rich medium containing CCCP was transferred to medium containing sucrose, its growth stopped for a while and then started again. This lag time was negligible in the absence of CCCP. The same results were obtained when the osmolarity was increased by N-methylglucamine-maleic acid. In addition to adapting itself to the hyperosmotic rich medium, E. coli adapted itself to hyperosmolarity in a minimal medium containing CCCP, again with a lag time. Hyperosmotic shock decreased the internal level of potassium ion rather than causing the accumulation of external potassium ion in the presence of CCCP. The internal amount of glutamic acid increased in cells growing in hyperosmotic medium in the presence and absence of CCCP. Large elevations in levels of other amino acids were not observed in the cells adapted to hyperosmolarity. Trehalose was detected only in hyperosmosis-stressed cells in the presence and absence of CCCP. These results suggest that E. coli can adapt to changes in the environmental osmolarity with a negligible accumulation of osmolytes from the external milieu but that the accumulation may promote the adaptation.
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The effects of major ischaemic metabolites on the fine structure of false tendon Purkinje cells from the dog heart were investigated in vitro under oxygenated and oxygen-deficient conditions. High levels of potassium ion induced potentially reversible alteration consisting of moderate cell swelling, swelling of sarcoplasmic reticulum, and nuclear swelling with moderate aggregation of chromatin irrespective of gas tension. Other metabolites induced alteration only in oxygen-deficient solutions. Ischaemic levels of lactate and inorganic phosphate both caused mitochondrial swelling, which was most severe in the presence of lactate. At acidic pH intramitochondrial dense inclusions, the hallmark of irreversible injury, also developed. Severe aggregation of nuclear chromatin and gross dilatations of the sarcoplasmic reticulum were focal and much less prominent than in contractile myocardium exposed to excess hydrogen ion. These observations indicate that the efflux of ischaemic metabolites from a developing infarct may be arrhythmogenic by impairing the function of the subjacent Purkinje network without damaging its cell structure, since luminal blood flow ensures it is always adequately oxygenated.
The kinetic and regulatory properties of homogeneous AMP deaminase from rat skeletal muscle have ben examined with particular emphasis on (a) the role of potassium ions in the expression of these properties and (b) the role of the adenylate energy charge in the regulation of AMP deaminase activity. Although the enzyme has an absolute requirement for K+, the concentration required for maximum activation is dependent on the concentration of substrate. At saturating levels of AMP (greater than or equal 2.0 mM) maximum activation is observed with 25 mM KCl, whereas at lower substrate concentrations (0.2 mM) approximately 50 mM KCl is needed for maximum activation. Conversely, the response of enzyme activity ot increasing levels of substrate is dependent on the level of potassium ions. At substrating concentrations of K+, the saturation curve for AMP is highly sigmoidal (nh=3.2) whereas at higher KCl concentrations, the apparent cooperativity between AMP sites is almost completely abolished (nh=1.5). The inhibition by a number of phosphorylated metabolites, including ATP, GTP, creatine-P, and P1, is likewise sensitive to the concentration of K+. These results suggest that a significant amount of interaction between K+ sites and both substrate and effector sites is required for the expression of the catalytic and regulatory properties of the enzyme. The specific effects of ATP, creatine-P, and P1 on the parameters of Km and Vmax indicate that each of these profile of AMP deaminase activity generated in response to variations in the adenylate energy charge shows that within the physiological range of energy charge (0.75 to 0.95), the activity increases linearly with decreasesing energy charge and is insensitive to both the total adenylate pool size and the presence of P1 and creatine-P. These data suggest that the most important factor in the regulation of AMP deaminase activity is the state of the energy charge rather than the absolute concentrations of the individual effectors.
We measured levels of potassium ion in the extracellular space of isolated superfused rabbit atria continuously with double-barreled microelectrodes of which on barrel was a K+ liquid ion-exchanger microelectrode and the other a potential-sensing micropipette. Increases in heart rate resulted in transient increases in extracellular potassium ([K+]0). When the quiescent atrium was stimulated the maximal increase was 0.4 mM at rates of 60/min, 0.7 mM at 90/min, 0.9 mM at 120/min, 1.3 mM at 200/min, and 1.8 mM at 300/min. The increase was not sustained during continued stimulation but declined toward prestimulation levels. When the stimulus was terminated the extracellular potassium activity decreased below bathing solution values by 0.2 mM after 60/min, 0.5 mM after 90/min, 0.7 mM ater 120/min, 0.9 mM after 200/min, and 1.0 mM after 300/min and subsequently returned to a value equal to that of the bathing solution. The magnitude of the decline in extracellular potassium activity during prolonged stimulation was markedly decreased when the bathing solution contained either zero potassium, ouabain, LiCl, or a decreased Po2 such that an elevation in [K+]0 persisted during stimulation. Moreover, the reduction in [K+]0 that followed the cessation of stimulation also was inhibited. These results support a role of the Na-K pump in maintaining extracellular potassium activity during changes in cardiac rate.
The main objective of the research is to study the effectiveness and safety of gossypol as a male contraceptive drug. Using a double-blind, randomized, controlled study design, gossypol was found to be an effective male antifertility drug, with no adverse effects on libido nor appetite. In terms of serum potassium levels, there were no statistical differences between gossypol and placebo groups at the end of the loading phase. However, through the ensuing 12 months of maintenance phase, a statistically significant trend toward reduced serum potassium level was evident.
In 1981 to 1983 we performed a clinical study with gossypol involving 152 participants, and in 1983 to 1985 we conducted another study of 120 participants. The first study was aimed at confirming gossypol's antifertility efficacy and determining the existence of side effects. The objective of the latter study was to find out whether the addition of a potassium salt supplement or a potassium-sparing agent could alleviate the side effect of hypokalemia. In both studies, the participants took a gossypol pill, 20 mg/day for 60 to 75 days for loading, and 50 mg/wk for maintenance. All participants were followed up for a year. The antifertility efficacy was found to be more than 90%, and the chief side effect was lowered serum potassium. In our 1983 to 1985 study, we concluded that since neither potassium supplementation nor triamterene solved the problem, it is very likely that gossypol is a nephrotoxic agent. With 1 year of gossypol treatment, serum testosterone and serum luteinizing hormone showed no change, whereas serum follicle-stimulating hormone showed some elevation after 6 months. The Shanghai researchers found that in their gossypol users, plasma and urinary beta 2-microglobulin levels were elevated to a certain extent. However, 25 subjects in our 1983 to 1985 study showed no appreciable change. Our volunteers had stopped taking gossypol for more than 1 year. In 1986 we started a third study, which was aimed at finding the lowest antifertility dose to minimize possible renal toxicity.
Serum and endometrial sodium (Na) and potassium (K) levels and serum estradiol, progesterone, testosterone and cortisol were measured in the mid-follicular and mid-luteal phases of the menstrual cycle in 20 Lippes loop and 20 CuT-200 IUCD users and 20 matched controls. Na and K were measured by atomic absorption spectrophotometry, while serum steroids were measured by RIA. Regarding steroids, the only significant difference between the three groups was a significantly lower mean mid-luteal serum estradiol in CuT-200 IUCD users compared to Lippes loop users (p less than 0.05). Regarding sodium in the control group, there was significantly lower mean mid-luteal serum and endometrial Na (p less than 0.01) that was not found in both groups of IUCD users. In the mid-follicular phase, there was significantly higher mean serum Na in both Lippes loop and CuT-200 groups compared to controls (p less than 0.05). Mean endometrial Na showed no significant difference between the three groups in both phases of the menstrual cycle. Regarding potassium in the control group, there was significantly lower mean levels in the mid-luteal-phase of the cycle (p less than 0.01) that was not seen with both groups of IUCD users. Serum K showed no significant difference in the three groups in both phases of the menstrual cycle. Endometrial K showed a significantly higher mean level in both Lippes loop and CuT-200 IUCD users compared to controls in the mid-luteal (p less than 0.01), but not in the mid-follicular phases of the cycle.