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PubMed1989

Automated quantitation of three-dimensional cardiac positron emission tomography for routine clinical use.

Visual comparison of rest/stress cardiac positron emission tomography indicates coronary flow reserve for diagnosing and assessing severity of coronary artery disease. An accurate, rapid, automated method for comparison and quantitation of paired cardiac PET studies has been developed to analyze size, intensity, statistical significance of and changes in perfusion or metabolism. The method utilizes polar coordinate maps derived from circumferential profiles of true short axis slices; from the short axis data algorithms determine mean and minimum activity levels in the anterior, septal, lateral, inferior and apical regions of the myocardium, percent of the cardiac image in specific ranges of activity levels or their changes and the percent of myocardium beyond 1.5, 2.0, and 2.5 standard deviations from the normal range with blackout display of the areas beyond these statistical limits for rest, stress, and stress/rest ratio polar maps. Additional applications include comparing stress-stress images to evaluate progression/regression of stenoses, early and late resting rubidium images for determining myocardial viability based on rubidium washout kinetics, and perfusion-metabolic comparisons for quantifying ischemia, viability and necrosis after acute myocardial infarction.

Algorithms↗
PubMed1988

[Disorders of plasma trace elements in diabetes. Relation to blood glucose equilibrium].

The influence of glycaemic control and diabetes characteristics on plasma concentrations of magnesium, zinc, copper, selenium, rubidium and bromine has been evaluated in 44 diabetics (30 insulin-dependent, 14 non insulin-dependent), and the results obtained were compared to those of 309 control subjects of the same mean age. Diabetics had reduced plasma magnesium concentrations (P less than 0.01) but normal erythrocyte magnesium levels. Plasma zinc and selenium concentrations were reduced, whereas those of copper were increased and those of bromine and rubidium were normal. Correlation between glycaemic control, evaluated by measurement of glycosylated haemoglobin levels, and each of the parameters studied was only demonstrated with magnesium in insulin-dependent diabetics (r = -0.561; P less than 0.02). No correlation was found with the other clinical or anthropometric characteristics of the diabetic patients studied. Diabetes seems to be associated with numerous abnormalities of plasma trace elements and magnesium, but the mechanism of these abnormalities has not yet been elucidated. A decrease in zinc and selenium concentrations and an increase in copper concentrations might be additional factors of atherogenicity.

Adult↗
PubMed1985

Maturation of Rb+ and PAH accumulation by rabbit anterior uvea and choroid plexus.

In vitro accumulation of radioactive para-aminohippuric acid (3H-PAH) and rubidium (86Rb+) by the anterior uvea, ciliary processes, and the choroid plexus was evaluated in tissues from newborn and various aged rabbits. Accumulation of PAH was present in the anterior uvea at 1 day of age (tissue to media ratio, T/M, of 2.1 +/- 0.2) and remained at this level for the first 14 days of life. Accumulation did not rise to adult levels until 21 days of age (T/M 5.5 +/- 0.6). Rubidium accumulation in the anterior uvea, a measure of Na+, K+-pump activity, was higher than adult values 6 hr after birth (T/M25.2 +/- 0.9). Activity remained elevated through day 28 and did not fall to adult levels until day 60 (T/M 13.4 +/- 0.6). Accumulation studies on isolated ciliary processes were similar to those obtained from anterior uveal tissue. Daily subcutaneous injections of penicillin (300,000 units/kg/day) for 1 week had no effect on anterior uvea PAH accumulation (penicillin T/M was 1.7 +/- 0.1 and saline control T/M was 2.0 +/- 0.2). Accumulation of either 3H-PAH or 86Rb+ by the choroid plexus was present 1 day after birth in amounts that were similar to adult values and did not change during the 90 days of testing.

Aminohippuric Acids↗
PubMed1985

Influence of fentanyl and morphine on intestinal circulation.

The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of 86Rb and 9-micron spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O2up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

Animals↗
PubMed1982

Brain tumor evaluation using Rb-82 and positron emission tomography.

Positron emission tomography of the brain with 75-sec rubidium-82 obtained from a portable generator (25-day Sr-82 leads to Rb-82) was used to evaluate the integrity of the blood-brain barrier (BBB) in patients with brain tumors. Rubidium is normally excluded from the central nervous system by the intact BBB, but when the BBB is disrupted by a tumor. Rb enters and pools in the extravascular spaces of the central nervous system. Since Rb is also rapidly cleared from the blood, a high tissue-to-blood ratio of the Rb-82 tracer is achieved in regions of BBB disruption after intravenous injection. With dynamic positron emission tomographic imaging, the extravasation of the Rb tracer can be evaluated independent of the intravascular Rb concentration, and very small changes in the BBB permeability can be detected. The results of our studies in eight patients show that this technique is a promising method for evaluation of the BBB integrity in brain-tumor patients.U

Adenocarcinoma↗
PubMed1984

The effect of an osmotic pressure gradient and lysophosphatidylcholine on the transient and constant potassium permeability properties of the erythrocyte membrane.

The rate constant of 86Rb efflux and total potassium release from erythrocytes under the influence of lysophosphatidylcholine (LPC) and osmotic pressure gradients were compared. Both osmotic pressure gradients and LPC caused a transient increase in the potassium permeability of the erythrocyte membrane. In hypotonic media without or in the presence of LPC this sudden increase is completely reversible, since the rate constant of rubidium efflux from unhaemolyzed cells, which is an indicator for the continuous potassium release, remained the same as measured in an isotonic NaCl medium without detergents. The potassium release was more pronounced in the presence of LPC and may have a protective effect against haemolysis. In an isotonic NaCl or sucrose medium, LPC caused a transient potassium release probably due to incorporation of LPC into the membrane and vesicle release, but also an increase in the rate constant of rubidium efflux due to change in the membrane structure connected with vesicle release.

Cell Membrane Permeability↗
PubMed1981

Sodium and water transport in frog skin: effect of indomethacin.

UNLABELLED: The transepithelial transport of sodium, rubidium and water was studied in the frog skin in the presence of the cyclic endoperoxidase inhibitor indomethacin. Sodium transport was studied by measuring short circuit current and by 24Na radioactive isotope method; water transport was examined using the frog skin sac technique. Indomethacin produced the following changes. 1. The transepithelial potential difference and the intensity of short circuit current were decreased, while the resistance and conductance of the skin remained unaltered. 2. Passive transepithelial sodium transport from the inner to the outer side was enhanced. 3. Neither osmotic water transport nor passive rubidium transport were changed. CONCLUSIONS: a) Indomethacin causes a selective increase of sodium permeability in the frog skin; b) The present results are in agreement with the view that the indomethacin may influence the rate of sodium transport in some tissues.

Animals↗
PubMed1995

Positron emission tomography in the diagnosis and management of coronary artery disease.

Positron emission tomography has grown rapidly from a little-understood research tool into an exciting noninvasive method for the clinician to evaluate myocardial perfusion, metabolism, and cell-membrane function. There are three radionuclides that are currently being used widely in cardiac positron emission tomography. These are nitrogen-13 ammonia, rubidium-82, and fluorine-18 fluordeoxyglucose. Nitrogen-13 ammonia and rubidium-82 are used to assess the severity and location of coronary artery disease, while fluorine-18 fluordeoxyglucose can identify impaired but viable myocardium, thus aiding in the subsequent management of these patients.

Ammonia↗
PubMed1994

Loop diuretics affect transcellular electrolyte transport in cells of the distal convoluted tubule.

Although loop diuretics act preferentially on sodium chloride absorption in the thick ascending limb of the loop of Henle in the nephron, high concentrations of some loop diuretics also impair sodium absorption in the distal convoluted tubule (DCT). To characterize further the inhibitory effect of these agents on sodium absorption in the DCT, the action of torsemide and furosemide on cell sodium, chloride and potassium concentrations was examined in individual DCT cells of the kidney cortex and also, for comparison, in proximal convoluted tubule cells. In addition, initial cell uptake rates of rubidium, an index of in vivo Na+/K(+)-ATPase activity, were studied. Both diuretics caused a significant reduction of intracellular sodium concentration and rubidium uptake in DCT cells but not in connecting tubule, principal, intercalated or proximal tubule cells. These findings are consistent with the concept that both diuretics reduce transcellular sodium absorption in DCT cells by impairing sodium entry across the apical cell membrane and, as a consequence, sodium extrusion by primary active Na+/K+ (Rb+) exchange across the basolateral membrane.

Animals↗
PubMed1993

Effects of competitive sodium-like antagonists on Na,K-ATPase suggest that cation occlusion from the cytoplasmic surface occurs in two steps.

Information on cation occlusion sites of renal NA,K-ATPase has been obtained by comparing the ability of competitive Na-like antagonists (David, P., Mayan, H., Cohen, H., Tal, D. M., and Karlish, S. J. D. (1992) J. Biol. Chem. 267, 1141-1149) with that of transported alkali metal cations to protect against covalent modification and structural perturbations of the protein. Sodium antagonists include p- or m-xylylenebisguanidium, guanidinium ions, and ethylenediamine. Experiments with proteoliposomes reconstituted with Na,K-ATPase demonstrate that p-xylylenebisguanidium has pronounced selectivity for the cytoplasmic surface. Tryptic digestion of Na,K-ATPase leading to "19-kDa membranes," a specifically truncated enzyme with intact cation occlusion sites, requires the presence of alkali metal cations. Sodium antagonists do not protect 19-kDa membranes against further digestion, and occlusion is destroyed. Incubation of 19-kDa membranes at 37 degrees C, in the absence of occluded ions, leads rapidly to loss of ability to occlude rubidium ions. Rubidium, sodium, or other alkali metal cations protect fully, whereas sodium antagonists do not protect against this thermal inactivation. Like the alkali metal cations, sodium antagonists protect Na,K-ATPase and, somewhat less effectively, 19-kDa membranes against inactivation by the carboxyl reagent N,N'-dicyclohexylcarbodiimide. Cation occlusion from the cytoplasmic surface is suggested to occur in two steps. In an initial recognition, either transported cations or sodium antagonists interact with carboxyl groups. The second step is selective for transported cations and involves occlusion of cations (either potassium or sodium ions) and a conformational change to a compact structure, which is resistant to proteolysis and thermal inactivation. Sodium antagonists are sterically hindered from becoming occluded and block Na,K-ATPase activity. Implications for the structural basis of cation specificity of the Na/K pump are discussed.

Animals↗
PubMed1998

Crystallization kinetics of a low-expansion feldspar glass for dental applications.

Previous studies have shown that the crystallization of glasses in the system K2O-Al2O3-SiO2, in the primary field of leucite, is not possible without modification of the composition. Leucite (KAlSi2O6) is used as a reinforcing phase in some compositions for all-ceramic dental restorations. However, because of their higher coefficient of thermal expansion, these materials cannot be veneered with conventional metal-ceramic porcelains. The purposes of this study were to investigate the crystallization behavior of a glass in the system K2O-Al2O3-SiO2 and to evaluate the effect of heat treatment on the crystal size, percent crystallinity, and coefficient of thermal expansion of the material. Ion-exchanged glass powder was prepared by mixing the glass with rubidium nitrate and heat-treating at 450 degrees C for 4, 8, 24, or 48 h. Bars were made from these powders and baked under vacuum at 1038 degrees C for 2 min. The bars made from the powder ion-exchanged for 48 h were further heat-treated for 4 h at either 800 degrees C, 850 degrees C, 900 degrees C, 950 degrees C, or 1038 degrees C. X-ray diffraction analyses showed cubic leucite was the only crystalline phase in the specimens made from the powders ion-exchanged for 4, 8, 24, or 48 h and baked at 1038 degrees C for 2 min. Further heat treatment for 4 h at either 800 degrees C, 850 degrees C, 900 degrees C, 950 degrees C, or 1038 degrees C promoted the growth of cubic leucite. In addition, a second phase identified as tetragonal rubidium-leucite was present in the specimens heat-treated for 4 h at 1038 degrees C. SEM observations showed that all specimens made from the powders ion-exchanged for 48 h exhibited small spherical crystals dispersed in a glassy matrix. The percent crystallinity ranged from 18.9% to 42.9% and the average particle size was between 0.64 to 1.18 microns. The coefficients of thermal expansion ranged between 8.076 and 8.788 x 10(-6)/degree C.

Aluminum Silicates↗
PubMed2001

Trimerization of alkali dicyanamides M[N(CN)2] and formation of tricyanomelaminates M3[C6N9] (M = K, Rb) in the melt: crystal structure determination of three polymorphs of K[N(CN)2], two of Rb[N(CN)2], and one of K3[C6N9] and Rb3[C6N9] from X-ray powder diffractometry.

The alkali dicyanamides M[N(CN)2] (M=K, Rb) were synthesized through ion exchange, and the corresponding tricyanomelaminates M3[C6N9] were obtained by heating the respective dicyanamides. The thermal behavior of the dicyanamides and their reaction to form the tricyanomelaminates were investigated by temperature-dependent X-ray powder diffractometry and thermoanalytical measurements. Potassium dicyanamide K[N(CN)2] was found to undergo four phase transitions: At 136 degrees C the low-temperature modification alpha-K[N(CN)2] transforms to beta-K[N(CN)2], and at 187degrees C the latter transforms to the high-temperature modification gamma-K[N(CN)2], which melts at 232 degrees C. Above 310 degrees C the dicyanamide ions [N(CN)2]- trimerize and the resulting tricyanomelaminate K3[C6N9] solidifies. Two modifications of rubidium dicyanamide have been identified: Even at -25 degrees C, the a form slowly transforms to beta-Rb[N(CN)2] within weeks. Rb[N(CN)2] has a melting point of 190 degrees C. Above 260 degrees C the dicyanamide ions [N(CN)2]- of the rubidium salt trimerize in the melt and the tricyanomelaminate Rb3[C6N9] solidifies. The crystal structures of all phases were determined by powder diffraction methods and were refined by the Rietveld method. alpha-K[N(CN)2] (Pbcm, a = 836.52(1), b = 46.90(1), c =7 21.27(1) pm, Z = 4), gamma-K[N(CN)2] (Pnma, a = 855.40(3), b = 387.80(1), 1252.73(4) pm, Z = 4), and Rb[N(CN)2] (C2/c, a = 1381.56(2), b = 1000.02(1), c = 1443.28(2) pm, 116.8963(6) degrees, Z = 16) represent new structure types. The crystal structure of beta-K[N(CN)2] (P2(1/n), a = -726.92(1), b 1596.34(2), c = 387.037(5) pm, 111.8782(6) degrees, Z = 4) is similar but not isotypic to the structure of alpha Na[N(CN)2]. alpha-Rb[N(CN)2] (Pbcm, a = 856.09(1), b = 661.711(7), c = 765.067(9) pm, Z = 4) is isotypic with alpha-K[N(CN)2]. The alkali dicyanamides contain the bent planar anion [N(CN)2]- of approximate symmetry C2, (average bond lengths: C-N(bridge) 133, C-N(term) 113 pm; average angles N-C-N 170 degrees, C-N-C 120 degrees). K3[C6N9] (P2(1/c), a = 373.82(1), b = 1192.48(5), c = 2500.4(1) pm, beta = 101.406(3) degrees, Z = 4) and Rb,[C6N9] (P2(1/c), a = 389.93(2), b = 1226.06(6), c = 2547.5(1) pm, 98.741(5) degrees, Z=4) are isotypic and they contain the planar cyclic anion [C6N9]3-. Although structurally related, Na3[C6N9] is not isotypic with the tricyanomelaminates M3[C6N9] (M = K, Rb).

Journal Article↗
PubMed1991

Proximal tubular cell sodium concentration in early diabetic nephropathy assessed by electron microprobe analysis.

Electron microprobe X-ray analysis techniques were employed in order to assess the changes that occur in proximal tubular cell sodium concentration during the hyperfiltration phase of early diabetes mellitus induced by streptozotocin in Sprague Dawley rats. Intracellular rubidium accumulation following intravenous infusion of rubidium chloride was used as a marker of basolateral Na/K-ATPase activity. The diabetic animals studied had a significantly higher glomerular filtration rate compared with controls [1.44 +/- 0.07 vs. 1.00 +/- 0.07 ml min-1 (100 g body weight)-1; mean +/- SEM, P less than 0.001]. Intracellular Na concentration was significantly higher in diabetic animals (19.5 +/- 0.6 vs. 17.8 +/- 0.4 mmol/kg wet weight; P less than 0.01). Concurrent measurement of Rb demonstrated significantly higher intracellular accumulation in the proximal tubules of diabetic animals compared with control (7.9 +/- 0.5 vs. 5.5 +/- 0.5 mmol/kg wet weight; P less than 0.001). These results indicate that proximal tubular Na/K-ATPase activity is enhanced in the hyperfiltration phase of diabetes mellitus. Since, however, intracellular Na concentration is increased under these conditions, it may be inferred that apical Na entry into proximal tubular cells is stimulated beyond the rate of basal exit during the initial development of hyperfiltration. The reasons for these alterations in cellular Na transport are unclear but similar changes have been implicated in the pathogenesis of cell growth.

Animals↗
PubMed1986

The anion specificity of the sodium-potassium-chloride cotransporter in rabbit kidney outer medulla: studies on medullary plasma membranes.

Plasma membrane vesicles were isolated from rabbit kidney outer medulla and employed in sodium, rubidium, and chloride flux studies. Chloride dependence and bumetanide sensitivity of (part of) the sodium and rubidium flux indicate that this plasma membrane fraction can be used to study the properties of Na-K-2Cl cotransport system present in the luminal membrane of the medullary thick ascending limb. The anion specificity of the cotransporter was investigated by determining the effect of anion replacement on sodium fluxes. When chloride was completely replaced by bromide, iodide, nitrate, or thiocyanate only bromide could effectively substitute for chloride (90% activity), whereas sodium uptake in the presence of iodide, nitrate, and thiocyanate amounted to only 25% of the sodium uptake observed in the presence of chloride. When similar replacement experiments were performed in the presence of 10 mmol/l chloride, bromide could substitute for chloride by 110%, iodide and nitrate by 60%, and thiocyanate by 70%. In the presence of 10 mmol/l bromide iodide, nitrate, and thiocyanate were similarly effective. The effect of nitrate and chloride on sodium flux was additive. Bumetanide-sensitive chloride uptake was inhibited by nitrate, the inhibition was however only partly, amounting to 60%. The results obtained are compatible with the view that the two anion binding sites of the Na-K-2Cl cotransporter can exhibit a different substrate specificity and that the transporter in addition to a 2Cl mode can also operate in a 2Br, Cl-, A- and Br-, A- mode, A- representing iodide, nitrate, or thiocyanate.

Animals↗
PubMed1976

Relationships between serosal medium potassium concentration and sodium transport in toad urinary bladder. III. Exchangeability of epithelial cellular potassium.

The exchangeability of toad bladder epithelial cell potassium has been investigated. An insignificant amount of cellular potassium exchanged with mucosal medium 42K. From the rate of uptake of 42K into the cells from the serosal medium at least two cellular potassium pools were identified. The more rapidly exchanging pool contained about one-quarter to one-third of the cellular potassium and exchanged with a half-time of about 30 min. It was from this pool that potassium was lost from cells exposed to ouabain or to a potassium-free medium. In addition, when 3.5 mM rubidium replaced 3.5 mM potassium in sodium Ringer's the epithelial cells lost in 60 min about one-quarter of their cellular potassium in exchange for rubidium. Inhibition of transepithelial sodium transport by amiloride, 10(-5) mM, seemed to depress the rate of potassium uptake into the more rapidly exchanging pool without affecting total cellular potassium content. However, stimulation of transepithelial sodium transport by vasopressin appeared not to affect the rate of potassium uptake. The rate of potassium uptake into this pool seemed much less than that required for a tight 1:1 coupling between transepithelial sodium transport and potassium uptake. The remaining cellular potassium exchanged at a much slower rate and even after 19 hours of incubation only 67% of cellular potassium was labelled. If this slower exchanging potassium represents a single pool, 99% of cellular potassium would be labelled only after incubation with 42K for 56 hours.

Animals↗
PubMed1981

Thallium interaction with the gastric (K, H)-ATPase.

The gastric (K, H)-ATPase has been shown to catalyze an electroneutral H+ for K+ exchange. Tl+ is able to substitute for K+ as an activating cation in the hydrolytic reaction with an apparent dissociation constant of 90 microM as compared to about 870 microM for K+. The ability of Tl+ to participate in transport is shown by the development of pH gradients in the presence of Tl+ following addition of ATP to gastric vesicles and by the ATP-dependent efflux of Tl+ from gastric vesicles. Inhibition of hydrolysis is observed at pH 7.4 with external Tl+ concentrations above 3.0 mM. This inhibition of hydrolysis is correlated with inhibition of pH-gradient formation. The inhibition of transport activity is partially relieved by a decrease in medium pH. This inhibitory effect is attributed to Tl+ binding at an external, low affinity cation site. In contrast to rubidium chloride, at high Tl+ concentrations, following the initial Tl+ efflux, there is reuptake of the cation. This rapid uptake is attributed to lipid-dependent Tl+ entry pathways. The vesicles exhibit a high permeability to thallium nitrate demonstrating a half-time (t1/2) for uptake of about 1.0 min in contrast to 46 min for rubidium chloride. In both gastric vesicles or liposomes, external Tl+ concentrations in excess of 1 to 4 mM are able to dissipate intravesicular proton gradients. Thus, although Tl+ is able to activate the gastric ATPase by mimicking K+, the permeability of this cation in lipid bilayers tends to uncouple H+ transport at concentrations high enough to generate detectable proton gradients.

Adenosine Triphosphatases↗
PubMed1988

The concentration of twelve elements in the anterior pituitary from human subjects and rats as measured by particle induced X-ray emission (PIXE).

The concentration of twelve elements--potassium, calcium, manganese, iron, cobalt, nickel, copper, zinc, arsenic, selenium, bromine, and rubidium--in anterior pituitaries from human subjects and rats was measured using Particle Induced X-ray Emission (PIXE). The human material included anterior pituitaries from 37 normal human subjects, 27 males and 10 females, all of whom died from traumatic lesions. Excluded from the investigations were persons with alcohol abuse, regular use of drugs, and babies younger than 1 year. For selenium, zinc, bromine, and to some extent copper, there was good correlation between the amounts found in anterior pituitaries from rats and human subjects. A significant difference between male and female rat pituitaries was observed for copper, iron, and rubidium, whereas for humans significant difference was only observed for manganese. Anterior pituitaries from human females contained generally more zinc than male glands, but the concentration of zinc in young males was higher than in females. The present study also indicates age related differences in the copper content in anterior pituitaries from human subjects, since pituitaries from humans between 15-45 years contained 25% more copper than those from younger or older persons. The opposite pattern was observed in males. For such elements as Cu, Fe, Mn, and Se, the content in the anterior pituitary from human subjects was 1.6-2 times that stated for other endocrine organs.

Adolescent↗
PubMed1985

Investigations of the action of the antitumour drug adriamycin on tumour cell membrane functions--I.

The membrane potential of L1210 murine leukemia cells was assessed by use of the tritiated lipophilic cation probe triphenylmethylphosphonium bromide. The potassium equilibrium potential of the cells was found to be -71 +/- 7 mV. The resting membrane potential was partly dissipated by the protonophore m-chlorocarbonylcyanidephenylhydrazone (10 microM), but was unaffected by ouabain (1 mM) and apparently by the calcium ionophore A23187 (2.5 microM). Monensin (20 microM) caused a hyperpolarization which, since it was blocked by ouabain, was presumed to be brought about by activation of the Na+K+-ATPase via an elevated cytoplasmic Na+ concentration. Adriamycin at concentrations as high as 5 X 10(-4) M brought about no change in the resting potential of the cells. Also, cytotoxic concentrations of adriamycin, unlike ouabain, had no effect on rubidium-86 transport into L1210 cells, nor upon a monensin-induced increased in rubidium-86 uptake. The results suggest that although adriamycin is capable of interaction with the plasma membrane, and may exert its cytotoxicity at this locus, changes in ion flux mediated by Na+K+-ATPase or those capable of changing the membrane potential do not appear to be implicated in its mechanism of action.

Animals↗