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Biomedical subjects

T Akera

Publications and source records attributed to T Akera.

At least 109 records · Page 6Linked to original sources
PubMed1979

Differential effect of potassium on the action of digoxin and digoxigenin in guinea-pig heart.

The effect of potassium on the binding of digoxin or digoxigenin to isolated Na+, K+-ATPase was compared with that of potassium on the positive inotropic action of the agents in guinea-pig hearts. The binding of digoxigenin to the enzyme in vitro was reduced to a greater extent by potassium than was the binding of digotoxin. The digoxigenin-induced increase in the force of contraction of left atrial preparations estimated at steady state was reduced at higher potassium concentrations. Potassium had a lesser effect when digoxin was used as the inotropic agent. In contrast, potassium concentrations. Potassium had a lesser effect when digoxin was used as the ininotropic agent. In contrast, potassium reduced the rate of development and also the rate of loss of the positive inotropic action of digoxin observed with left atrial and Langendorff preparations, respectively, to a greater extent than those of digoxigenin. The loss of the positive inotropic effect was more rapid with digoxigenin than with digoxin at each KCl concentration. These data support the contention that the extent of the interaction of digitalis with Na+,K+-ATPase determines the degree of the positive inotropic effect.

Animals↗
PubMed1979

Sodium influx rate and ouabain-sensitive rubidium uptake in isolated guinea pig atria.

1. Ouabain-sensitive 86Rb+ uptake by tissue preparations has been used as an estimate of Na+ pump activity. This uptake, however, may be a measure of the Na+ influx rate, rather than capacity of the Na+ pump, since intracellular Na+ concentration is a determinant of the active Na+/Rb+ exchange reaction under certain conditions. This aspect was examined by studying the effect of altered Na+ influx rate on ouabain-sensitive 86Rb+ uptake in atrial preparations of guinea pig hearts. 2. Electrical stimulation markedly enhanced ouabain-sensitive 86Rb+ uptake without affecting nonspecific, ouabain-insensitive uptake. Paired-pulse stimulation studies indicate that the stimulation-induced enhancement of 86Rb+ uptake is due to membrane depolarizations, and hence related to the rate of Na+ influx. 3. Alterations in the extracellular Ca2+ concentration failed to affect the 86Rb+ uptake indicating that the force of contraction does not influence 86Rb+ uptake. 4. Reduced Na+ influx by low extracellular Na+ concentration decreased 86Rb+ uptake, and an increased Na+ influx by a Na+-specific ionophore, monensin, enhanced 86Rb+ uptake in quiescent atria. 5. Grayanotoxins, agents that increase transmembrane Na+ influx, and high concentrations of monensin appear to have inhibitory effects on ouabain-sensitive 86Rb+ uptake in electrically stimulated and in quiescent atria. 6. Electrical stimulation or monensin enhanced ouabain binding to (Na+ + K+)-ATPase and also increased the potency of ouabain to inhibit 86Rb+ uptake indicating that the intracellular Na+ available to the Na+ pump is increased under these conditions. 7. The ouabain-sensitive 86Rb+ uptake in electrically stimulated atria was less sensitive to alterations in the extracellular Na+ concentration, temperature and monensin than that in quiescent atria. 8. These results indicate that the rate of Na+ influx is the primary determinant of ouabain-sensitive 86Rb+ uptake in isolated atria. Electrical stimulation most effectively increases the Na+ available to the Na+ pump system. The ouabain-sensitive 86Rb+ uptake by atrial preparations under electrical stimulation at a relatively high frequency seems to represent the maximal capacity of the Na+ pump in this tissue.

Animals↗
PubMed1979

Increase in Na+, K+ -ATPase enzyme units in liver and kidneys from essential fatty acid deficient rats.

(3H)-Ouabain binding to liver and kidney preparations was utilized to estimate the number of Na+, K+-ATPase enzyme units in livers and kidneys from rats fed 2% corn oil supplemented or fat-free diets. The specific (3H)-ouabain binding in liver and kidney preparations from fatty acid deficient rats was increased approximately 40%, but the affinity of the binding sites for ouabain (Kd-value) remained unchanged. The increased concentration of Na+, K+-ATPase enzyme units observed in the essential fatty acid deficient rats may contribute to the reduced body fat accumulation and elevated heat production observed in these animals.

Animals↗
PubMed1979

Effects of monovalent cations on (Na+ + K+)-ATPase in rat brain slices.

The influence of monovalent cations on membrane (Na + K+)-ATPase was estimated in vitro in intact cells from the oxygen consumption of rat brain cortical slices. High concentrations of K+, Rb+ or Cs+ stimulated the respiration in the presence of Na+. This stimulation was antagonized by ouabain in a concentration- and time-dependent manner. Additionally, only combinations of monovalent cations, that stimulate (Na+ + K+)-ATPase, increased oxygen consumption, indicating that the stimulated portion of respiration is realted to the (Na+ + K+)-ATPase activity. Low concentrations of Rb+ and Cs+, however, failed to affect oxygen consumption. Li+ slightly and transiently stimulated oxygen uptake at low concentrations and inhibited it at higher concentrations. Low concentrations of Tl+ also stimulated respiration in a K+-free medium. However, the inhibitory effects of Tl+ were predominant at higher concentrations or in the presence of K+. Thus, monovalent cations can alter (Na+ + K+)-ATPase activity. While Rb+ and Li+ produce opposite effects on this enzyme system under certain conditions, these actions do not seem to be related to the antidepressant action of Rb+ and the antimanic action of Li+.

Animals↗
PubMed1979

Saturable adenosine 5'-triphosphate-independent binding of [3H]-ouabain to brain and cardiac tissue in vitro.

1. Several investigators have proposed that membrane Na+, K+-adenosine 5'-triphosphatase (Na+, K+-ATPase) is a mechanism for the transmembrane transport of cardiac glycosides, rather than the receptor for pharmacological actions of these agents. This implies that the glycosides bind to an intracellular constituent (receptor) other than Na+, K+-ATPase. 2. In search for such a receptor site, saturable ATP-independent [3H]-ouabain binding was studied in rat brain and dog and guinea-pig heart homogenates. The binding of the glucoside to this site results in a relatively unstable complex which is stabilized by K+ to a lesser extent than is the complex formed with the ATP-dependent binding to Na+, K+-ATPase. 3. The ATP-independent ouabain binding sites are more abundant in rat brain tissue than in cardiac tissue, and have a lower ouabain affinity compared to the binding sites on Na+, K+-ATPase. 4. These results do not support the contention that there are intracellular inotropic receptors for digitalis.

Adenosine Triphosphate↗
PubMed1979

Na+,K+-ATPase enzyme units in lean and obese (ob/ob) thyroxine-injected mice.

The possible involvement of Na+,K+-ATPase in the etiology of obesity in the obese (ob/ob) mouse was explored. The number of Na+,K+-ATPase enzyme units in skeletal muscle, liver, and kidneys from 4- and 8-wk-old obese and lean mice was estimated from saturable [3H]ouabain binding to particulate fractions. Neither phenotype nor age altered the Kd value for ouabain binding in these three tissue preparations. The total number of [3H]ouabain binding sites in hindlimb muscles was 35--55% lower in 4- and 8-wk-old obese mice than in their lean counterparts. However, the total number of [3H]ouabain binding sites in liver and kidneys of obese mice was similar to values observed in their lean counterparts. Because it has been suggested that ob/ob mice are hypothyroid, we investigated the response of Na+,K+-ATPase in these mice to thyroid hormone treatment (approximately 5 microgram thyroxine/day for 2 wk). The number of [3H]ouabain binding sites in the three tissues increased in both obese and lean mice injected with this relatively large dose of thyroxine, but the obese mice were 2--3 times more responsive than lean mice.

Age Factors↗
PubMed1979

Reduction of opiate binding to brainstem slices associated with the development of tolerance to morphine in rats.

Previous studies revealed that the characteristics of opiate binding sites are different in brainstem slices and homogenates. In the present study, the binding of opiate agonists, morphine and etorphine, and that of the antagonist, naloxone, to thin slices of rat brain stem was studied. Sodium ion inhibits agonist binding and enhances antagonist binding in brainstem slices. Development of the analgesic tolerance to morphine is accompanied by a reduction of opiate binding. The opiate binding recovers partially toward control values during morphine withdrawal. Kinetic analyses indicate that sodium-induced changes in opiate binding sites are different from those caused by chronic morphine treatment. These results provide evidence that analgesic tolerance is associated with changes in opiate receptors.

Analgesics↗
PubMed1978

Prednisolone-3, 20-bisguanylhydrazone: Na+, K+-ATPase inhibition and positive inotropic action.

The relationship between two known actions of prednisolone-3, 20-bisguanylhydrazone (PBGH); Na+, K+-ATPase inhibition and positive inotropic effects, was investigated. In electrically driven left atrial preparations of guinea pig heart, the positive inotropic action of PBGH was not affected by beta-adrenergic or histamine antagonists. Pretreatment of animals with reserpine also failed to influence the positive inotropic action of PBGH. Inotropic concentrations of PBGH inhibited Na+, K+-ATPase and the ATP-dependent binding of (3/)-ouabain to Na+, K+- ATPase preparations in vitro. Additionally, ouabain-sensitive 86Rb uptake, an estimate of sodium pump activity was inhibited when sodium-loaded ventricular slices were obtained from Langendorff preparations at the peak inotropic response to PBGH. Guinea pig heart was highly sensitive to PBGH to the positive inotropic action, the inhibition of Na+, K+ -ATPase and (3H)-ouabain binding, whereas rat, rabbit and dog heart were markedly less sensitive. These findings suggest that the mechanism of the positive inotropic action of PBGH resembles that of ouabain and probably involves Na+, K+ -ATPase inhibition, although the mode of interaction of these steroids with Na+, K+ -ATPase may be different.

Adenosine Triphosphatases↗
PubMed1978

Membrane (Na+ + K+)-ATPase of canine brain, heart and kidney. Tissue-dependent differences in kinetic properties and the influence of purification procedures.

Effects of commonly used purification procedures on the yield and specific activity of (Na+ + K+)-ATPase (Mg2+-dependent, Na+ + K+-activated ATP phosphohydrolase, EC 3.6.1.3), the turnover number of the enzyme, and the kinetic parameters for the ATP-dependent ouabain-enzyme interaction were compared in canine brain, heart and kidney. Kinetic parameters were estimated using a graphical analysis of non-steady state kinetics. The protein recovery and the degree of increase in specific activity of (Na+ + K+)-ATPase and the ratio between (Na+ + K+)-ATPase and Mg2+-ATPase activities during the successive treatments with deoxycholate, sodium iodide and glycerol were dependent on the source of the enzyme. A method which yields highly active (Na+ + K+)-ATPase preparations from the cardiac tissue was not suitable for obtaining highly active enzyme preparations from other tissues. Apparent turnover numbers of the brain (Na+ + K+)-ATPase preparations were not significantly affected by the sodium iodide treatment, but markedly decreased by deoxycholate or glycerol treatments. Similar glycerol treatment, however, failed to affect the apparent turnover number of cardiac enzymes preparations. Cerebral and cardiac enzyme preparations obtained by deoxycholate, sodium iodide and glycerol treatments had lower affinity for ouabain than renal enzyme preparations, primarily due to higher dissociation rate constants for the ouabain.enzyme complex. This tissue-dependent difference in ouabain sensitivity seems to be an artifact of the purification procedure, since less purified cerebral or cardiac preparations had lower dissociation rate constants. Changes in apparent association rate constants were minimal during the purfication procedure. These results indicate that the presentyl used purification procedures may alter the properties of membrane (Na+ + K+)-ATPase and affect the interaction between cardiac glycosides and the enzyme. The effect of a given treatment depends on the source of the enzyme. For the in vitro studies involving purified (Na+ + K+)-ATPase preparations, the influence of the methods used to obtain the enzyme preparation should be carefully evaluated.

Adenosine Triphosphatases↗
PubMed1978

Increased (Na+,K+)-ATPase concentrations in various tissues of rats caused by thyroid hormone treatment.

Effects of triiodothyronine treatment on (Na+,K+)-ATPase in the brain, liver, kidney, and skeletal muscle were studied in the rat. The number of (Na+,K+)-ATPase units in the particulate fractions obtained from deoxycholate-treated homogenates was estimated from the concentration of [3H]ouabain binding sites assayed with a labeled drug-displacement method. The concentration of [3H]ouabain binding sites was highest in the brain tissue, intermediate in the kidney, and relatively low in the liver and skeletal muscle. The affinity of the binding sites for ouabain was highest in the brain, intermediate in the skeletal muscle, low in the kidney, and lowest in the liver. Triiodothyronine treatment increased the [3H]ouabain binding site concentration in the liver, kidney, and skeletal muscle but failed to affect it in the brain. Affinity of the binding sites for ouabain was unchanged by the triiodothyronine treatment in all tissues studied. These data indicate that triiodothyronine treatment of rats results in an increased tissue concentration of (Na+,K+)-ATPase in the liver, kidney, and skeletal muscle, but not in the brain. These changes do not accompany marked changes in the characteristics of the enzyme.

Adenosine Triphosphatases↗
PubMed1978

Reduction of the equilibrium binding of cardiac glycosides and related compounds to Na+,K+-ATPase as a possible mechanism for the potassium-induced reversal of their toxicity.

The influence of potassium ions on the equilibrium state of the binding of cardiac glycosides and their derivatives to partially purified dog heart and rat brain enzyme preparations was studied in vitro. The addition of potassium to the incubation mixture containing enzyme preparation, 3H-ouabain, Na+, Mg2+ and ATP, at the time when the binding reaction is close to equilibrium, caused an immediate reduction of the bound drug concentration; the concentration apparently shifting toward a lower equilibrium state. The degree of the potassium-induced reduction in bound drug concentration was dependent on the potassium concentration and on the chemical structure of the compound. The binding of aglycones, pentacetyl-gitoxin and cassaine was affected to a greater extent than that of the glycosides. These data suggest that one of the mechanisms by which potassium antagonizes the toxic actions of digitalis on the heart is to reduce the drug binding to cardiac Na+,K+-ATPase.

Animals↗
PubMed1978

Effects of lithium and thallous ions on sodium pump activity in the guinea-pig heart and their relationship to the positive inotropic action.

It has recently been demonstrated that both Tl+ and Li+ produce concentration- and time-dependent positive inotropic effects in guinea-pig atrial preparations although Tl+ inhibits and Li+ stimulates isolated Na+,K+-ATPase in vitro. In order to elucidate the mechanism of the positive inotropic actions of these cations, the effects of Tl+ and Li+ on sodium pump activity were studied. Active 86Rb uptake in guinea-pig ventricular slices, an estimate of sodium pump activity, was highly sensitive to the inhibitory effect of the cardiac glycosides. Preincubation of slices with Tl+ caused a dose- and time-dependent inhibition of active 86Rb uptake. Similar concentration- and time-dependent inhibition of active 86Rb uptake was observed when Na+ in a Krebs-Henseleit solution was partially replaced with Li+. Lithium, however, stimulated a partially purified Na+,K+-ATPase in vitro. During heart slice incubation, Tl+ and Li+ accumulated in a time-dependent manner. This accumulation was not readily reversible when slices were transferred into Tl+- or Li+-free solutions. It appears that the inhibition of sodium pump activity is related to the positive inotropic action of these cations.

Animals↗