[Anthraquinones and anthraquinone glycosides. 19. Synthesis of alpha and beta frangulin and frangula-emodin-9-anthron-10-C-glycoside].
Explore the source record for details and available documents.
Aloe↗
SEARCH · Search PubMed
Results for “GLYCOSIDES”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Synthesis and study of N-glycosides. IV. N-glycosides of m-aminoacetophenone].
Explore the source record for details and available documents.
Acetophenones↗
Temporal and spatial variation in cyanogenic glycosides in Eucalyptus cladocalyx.
The release of hydrogen cyanide from endogenous cyanide-containing compounds in plants is an effective herbivore deterrent. We investigated temporal and spatial variations in cyanogenic glycoside concentration in greenhouse-grown seedlings and 6-year-old plantation trees of Eucalyptus cladocalyx F. Muell., which allocates up to 20% of leaf nitrogen to the cyanogenic glycoside, prunasin. The highest cyanogenic glycoside concentrations were in the young, developing vegetative and reproductive tissues. Both the overall cyanogenic glycoside concentration and the proportion of nitrogen allocated to cyanogenic glycoside decreased as tissues matured. Cyanogenic glycoside and nitrogen concentrations were similar at all positions on the leaf blade. There was no change in concentration of cyanogenic glycosides either diurnally or following wounding of the tissue, suggesting that these compounds are constitutive. Cyanogenic glycoside concentration varied seasonally in young leaf tips of field-grown E. cladocalyx, but not in mature, fully expanded leaves. Although some of the changes in cyanogenic glycoside concentration in young leaf tips may have been driven by changes in leaf nitrogen, there was a significant decrease in the proportion of nitrogen allocated to cyanogenic glycosides in young leaves during the summer, coinciding with the peak flowering period. Mobilization of cyanogenic glycosides may have occurred to provide nitrogen for reproduction. Most of the observed temporal and spatial variations in cyanogenic glycosides are consistent with the optimal use of resources, particularly nitrogen.
Journal Article↗
Study of the collision-induced radical cleavage of flavonoid glycosides using negative electrospray ionization tandem quadrupole mass spectrometry.
Negative electrospray ionization tandem quadrupole mass spectrometry was used to study the collision-induced dissociation (CID) of the O-glycosidic bond from different commercially available flavonoid glycosides. Depending on the structure, flavonoid glycosides can undergo both a collision-induced homolytic and heterolytic cleavage of the O-glycosidic bond producing deprotonated radical aglycone ((Y(0) - H)(-*)) and aglycone (Y(0) (-)) product ions. The relative abundance of the radical aglycone to the aglycone fragment from flavonol-3-O-glycosides increased with increasing number of hydroxyl substituents in the B ring and in the order kaempferol - <quercetin - <myricetin-3-O-glycoside. The nature and position of the sugar substitution of the flavonol glycosides also affected the fragmentation to the radical aglycone. Obtained under similar conditions, the product ion spectrum of kaempferol-7-O-neohesperidoside showed only a minor radical aglycone product ion as opposed to kaempferol-3-O-rutinoside. The relative abundance of the radical aglycone to the aglycone fragment from flavone-7-O-glycosides was also dependent on the substitution in the B ring. CID of apigenin-7-O-glucoside produced relatively more of the radical aglycone fragment than luteolin-7-O-glucoside, while only the aglycone fragment was found from diosmetin-7-O-rutinoside. The position of the sugar substitution also affected the fragmentation of the flavone glycosides, such that the product ion spectrum of luteolin-4'-O-glucoside showed only the aglycone fragment as opposed to luteolin-7-O-glucoside. No radical aglycone fragments were found from the flavanone-7-O-glycosides and dihydrochalcone glycoside investigated in the study.
Chalcone↗
Effect of diets fortified with tomatoes or onions with variable quercetin-glycoside content on azoxymethane-induced aberrant crypt foci in the colon of rats.
BACKGROUND: Onion and tomato are vegetables widely consumed by humans and epidemiological studies show an inverse association between vegetable consumption and colon cancer risk; however, the effect on colon cancer of diets containing high levels of vegetables like onion and tomato are not clear. AIMS OF THE STUDY: To investigate whether tomatoes and onions,with low or high quercetin-glycoside content, could reduce azoxymethane (AOM)-induced Aberrant Crypt Foci (ACF), preneoplastic lesions in the colon of rats. METHODS: Male Fisher 344 rats were fed the following diets: a) high fat (HF) diet (control diet); b) HF diet containing 20 % (w/w) tomatoes with a low quercetin-glycoside content (final concentration in the diet: 5 mg/kg of quercetin aglycone equivalents); c) HF diet containing 20% (w/w) high quercetin-glycoside tomatoes (100 mg/kg final concentration of quercetin aglycone equivalents); d) HF diet containing 20 % (w/w) low quercetin-glycoside onions (14 mg/kg of quercetin aglycone equivalents in the diet); e) HF diet containing 20 % (w/w) high quercetin-glycoside onions (360 mg/kg quercetin aglycone equivalents in the diet). After 2 wks of feeding, all rats were treated twice, 1 wk apart, with AOM (12 mg/kg, s. c.). The dietary treatments continued until sacrifice, 7 wks after the first injection with AOM. RESULTS: ACF induction did not vary in animals fed low or high quercetin-glycoside tomatoes relative to controls. On the contrary, rats fed 20% (w/w) onion-based diets, with low or high quercetin-glycoside content, showed an increase in number, multiplicity and "large" ACF compared to the control group (number of ACF/colon 145 +/- 15 (SE), 255 +/- 11 and 218 +/- 16 in controls, low and high-quercetin-glycoside groups, respectively; p < 0.01). Proliferative activity of the colon did not vary between animals fed control and high quercetin-glycoside tomato diet. The height of the crypts in normal mucosa of rats fed high quercetinglycoside onions was significantly increased compared to control rats (cells/emicrypt 38.4 +/- 1.2 (SE) and 41.3 +/- 0.6 in controls and high quercetin-glycoside onions group, p < 0.05). CONCLUSIONS: None of the diets supplemented with onion or tomato with variable quercetin-glycoside content demonstrated a potential chemopreventive effect on ACF-induction by AOM in rats.
Animals↗
Studies on the localization of the cardiac glycoside receptor.
The purpose of this study was to see whether the receptor for cardiac glycosides might be localized upon or within the plasma membrane of digitalis-sensitive cells. Ouabain and digoxin were joined covalently to several large protein molecules. These macromolecular conjugates are too large to enter intact cells; consequently, any pharmacologic or biochemical effects which they display should arise from interaction with a cell surface receptor. Conjugates were tested in several cardiac glycoside-sensitive systems: (a), contractility response of isolated cardiac muscle; (b), active (86)Rb(+) uptake by red cells; (c), enzymatic activity of isolated myocardial microsomal (Na(+) + K(+))-activated adenosine triphosphatase (ATPase); and (d), enzymatic activity of solubilized red cell (Na(+) + K(+))-activated ATPase. Results demonstrated that in all of these systems, the macromolecular-glycoside conjugates were 100- to 1000-fold less active than the free glycosides. Careful chromatographic examination of the various conjugates revealed that they contained a small but persistent free cardiac glycoside contaminant. The amount of this species ranged from 0.1 to 1.0% of the total macromolecule-bound glycoside, and its presence fully explains the levels of biologic activity observed with the conjugates. To try to minimize steric factors which could interfere with glycoside-receptor interaction, digoxin and ouabain were also coupled to macromolecule via long, flexible polyamide side-chains. These extended chain conjugates, in which the cardiac glycoside potentially lay some 30 A removed from the surface of the macromolecule, also exhibited negligible digitalis-like effects when tested upon isolated cardiac muscle, red cell (86)Rb(+) uptake, and enzymatic activity of cardiac microsomal (Na(+) + K(+))-ATPase. However, the extended chain conjugates were fully active when examined with the solubilized red cell (Na(+) + K(+))-ATPase system. To further ensure that the chemical reactions used to couple macromolecule to glycoside did not inactivate the drug, all conjugates were subjected to extensive proteolytic digests exhibited full pharmacologic activity. Digoxin was also coupled to the tripeptide alanylglycylglycine, and the resulting conjugate was fully active. Taken together, these results suggest that if the receptor(s) for cardiac glycosides is associated with the plasma membrane, then it may lie deep within it.
Adenosine Triphosphatases↗
[Partial purification and use of Trypanosoma cruzi glycosidic fractions for Chagas disease diagnosis].
Protein and glycoprotein fractions are used for Chagas' disease diagnosis, but they are degraded by parasite endogenous proteases. Therefore protease inhibitors are used for their conservation increasing the antigen cost. The possibility of using protease-resistant glycosidic fractions could solve this problem allowing to obtain stable antigens, with a high sensitivity at a lower cost. This proposal is reinforced by the existence of anti-galactosyl antibodies against T. cruzi oligosaccharic fractions in sera from chagasic patients. The aim of this work was to obtain T. cruzi glycosidic fractions and to evaluate their possible use for Chagas' disease serologic diagnosis. Total protein and glycoproteins from the four stages of T. cruzi were obtained. The glycosidic fractions were obtained by exhaustive proteolysis with Proteinase K. Protein, glycoprotein and glycosidic profiles were analysed by SDS-PAGE followed by staining proteins (Coomassie/silver) or glycoproteins and glycosidic fractions (APABGP). Antigenicity of the different fractions was determined by Western Blot and luminography, using control hyperimmune serum anti-epimastigote and a "pool" of chagasic human sera. Finally, the capacity of the glycosidic fractions to discriminate chagasic and non-chagasic human sera and the sensitivity of the fractions respect to control serum, were determined by ELISA. Main findings were: a) there are peptides, glycopeptides and glycosidic fractions that are common and specific to parasite stages; b) there are more antigenic glycoproteins in epimastigotes and metacyclics than in trypomastigotes and amastigotes; c) there is a correlation between the glycosidic fraction-pattern and the host type; d) glycosidic fractions can be used as antigens to discriminate, by ELISA, chagasic and non chagasic patients, but show lower titers with respect to total proteic and glycoprotein antigens. It is concluded that it is possible to develop a diagnostic kit for Chagas' disease employing glycosidic fractions, eliminating the disadvantages of the current kits.
Animals↗
Changes in histamine secretion from mast cells caused by digitalis glycosides.
Cardiotonic glycosides modify histamine secretion from rat mast cells in the following way. (1) Preincubation (30 min) of mast cells with liposoluble glycosides (10(-4) mol/l) increases the spontaneous histamine secretion by about 5%. (2) Preincubation of mast cells with 10(-4) mol/l liposoluble glycosides (digitoxin, digoxin, digitoxigenine) decreases histamine release induced by compound 48/80 in the presence of calcium, whereas the water soluble glycoside, strophanthin G, has no effect on the secretion. (3) Preincubation of mast cells in a calcium-free medium with the glycosides (10(-4) mol/l) has a dual-effect on histamine secretion induced by compound 48/80: water soluble glycosides (strophanthin G and K) potentiate histamine release, whereas the liposoluble glycosides (digitoxin, digitoxigenine) decrease the secretory response. The difference in the activity of different glycosides could be explained by their dual effects, namely an inhibition of Na+K(+)-ATPase which leads to an increase in histamine release, and intracellular action(s) of liposoluble glycosides leading to a decrease of histamine secretion.
Animals↗
Estimation of aroma glycosides of nutmeg and their changes during radiation processing.
Glycosidically bound volatile compounds of nutmeg were identified as glyco-conjugates of p-cymene-7-ol, eugenol, methoxyeugenol and alpha-terpineol. Using phenyl-beta-glucoside as external standard the contents of these glycosidic precursors were estimated based on the measurement of TLC spot density on a densitometer. p-Cymene-7-ol rutinoside was the major aroma glycoside (3.15 mg/100 g), followed by glucosides of methoxyeugenol (0.61 mg/100 g), eugenol (0.50 mg/100 g) and alpha-terpineol (0.51 mg/100 g). A dose-dependent breakdown of these glycosidic precursors was observed during gamma-radiation processing. Among the four glycosides, alpha-terpineol glucoside was the most sensitive to radiation while p-cymene-7-ol rutinoside was the least sensitive. A reduction in the content of total glycosides by almost 50% was noted at a dose of 5kGy. Partitioning of aroma glycoside into n-butanol from aqueous extracts was found to result in rapid isolation of aroma glycosides, avoiding time consuming pre-purification on Amberlite XAD-2 column. A routine method based on extraction into n-butanol and subsequent quantification of post-irradiation changes in aroma glycosides on a TLC plate using a densitometer is proposed.
Chromatography, Thin Layer↗
Screening and identification of glycosides in biological samples using energy-gradient neutral loss scan and liquid chromatography tandem mass spectrometry.
A rapid, selective, and reliable strategy has been developed for the screening and identification of glycosides in biological samples: a crude extract was directly infused to a triple-quadrupole MS/MS, and major glycosides were screened out with high confidence by an energy-gradient neutral loss scan (EGNLS) for the loss of sugar(s); then these glycosides were further identified with LC/MS/MS. The proposed EGNLS method was established and optimized with 16 representative glycosides (including ginsenosides and the glycosides of flavones, anthraquinones, and terpenoids). The EGNLS method has two major advantages over the conventional fixed-energy neutral loss scan: (1) The latter is liable to '"omit" some target compounds due to the usual mismatch between the preset collision energy and interested compounds' optimal collision energy (OCE), while EGNLS solves this problem by scanning over an energy range. (2) The EGNLS simultaneously measures the screened compounds' OCE, which not only are essential parameters for further LC/MS/MS analysis but also carry some structural information, as proved by this study. This strategy has been successfully demonstrated with the analysis of glycosides in Scutellaria viscidula Bge and transformed Panaxhairy roots (the glycoside constitutions of both had not been studied before): without laborious separation processes; comprehensive glycoside information on those two plants was obtained by a rapid and simple procedure. This strategy is valuable for the study of glycosides in complex samples.
Chromatography, High Pressure Liquid↗
Differentiation of interglycosidic linkages in permethylated flavonoid glycosides from linked-scan mass spectra (B/E).
A series of per-O-methylated flavonoid di- and tri-glycosides, linked with 1-2 and/or 1-6 glycosidic bonds between sugar rings that were isolated from different plant materials were analyzed. It was demonstrated that the fragmentation behavior of permethylated flavonoid glycosides is dependent on the glycosidic bond placement between sugars. Y(n) type fragment ions, created after glycosidic bond cleavage with oxygen retention on sugar at the reducing end for permethylated compounds, were observed in the normal and linked-scan mass spectra recorded for alpha(1-2) bonded conjugates of flavonoid di- and tri-glycosides. Moreover, for alpha (1-6) linked glycosides, Y fragments created after rearrangement and elimination of internal sugar residues were observed in addition to Y(n) type ions, but these fragment ions were not registered in normal desorption ionization spectra. This second type of fragmentation was also reported previously in collision-induced dissociation tandem mass spectrometry (CID MS/MS) spectra of some oligosaccharides and flavonoid glycosides, but their presence was independent of the glycosidic bonds placement between sugar rings.
Flavonoids↗
MALDI-TOF MS analysis of food flavonol glycosides.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a new technique that is having a great impact on food analysis. This study is the first to demonstrate the use of MALDI-TOF MS to identify flavonol glycosides in food samples. 2',4',6'-Trihydroxyacetophenone was chosen as the best matrix because it worked for crude sample extracts and ionized flavonol glycosides in both positive and negative MALDI-TOF MS modes. In the positive mode, multiple ion forms were observed for flavonol glycosides, including [M + H](+), [M + Na](+), [M + K](+), and [M - H + Na + K](+), with further fragmentation through loss of glycosidic residues. The negative mode for all flavonol glycosides resulted in [M - H](-) ion formation without detectable fragmentation. The multiple ions in the positive mode gave more information on individual flavonol glycoside structures than the negative mode. Flavonol glycosides showed similar intensities or responses in the positive mode, while kaempferol glycosides exhibited much less response than quercetin glycosides in negative mode.
Flavonoids↗
Triterpene glycosides from the Far Eastern sea cucumber Cucumaria conicospermium.
Four new triterpene glycosides, cucumariosides A(2)-5 (1), A(3)-2 (2), A(3)-3 (3), and isokoreoside A (4), along with the previously isolated koreoside A (5), have been found in the sea cucumber Cucumariaconicospermium. Glycoside 1 was isolated as a native substance, while glycosides 2-5 were identified through their desulfated derivatives. Their structures have been deduced by extensive spectral analysis (NMR and MS) and chemical evidence. All the glycosides contain the same branched pentasaccharide carbohydrate chain but differ in the number and positions of the sulfate groups. Glycoside 1 has one, glycosides 2 and 3 have two, and glycosides 4 and 5 have three sulfate groups. Glycosides 2-5 are non-holostane derivatives; their aglycons lack the 18(20)-lactone and are characterized by shortened side chains, which is a very rare feature among the sea cucumber glycosides.
Animals↗
Preparation of oligomeric beta-glycosides from cellulose and hemicellulosic polysaccharides via the glycosyl transferase activity of a trichoderma reesei cellulase.
Oligoglycosyl (allyl, 2,3-dihydroxypropyl, ethyl, 2-hydroxyethyl, and methyl) beta-glycosides were generated by endo -transglycosylation reactions catalyzed by commercially available Trichoderma reesei cellulase. A polymeric donor substrate (xyloglucan or cellulose) was incubated with the enzyme in an aqueous solution containing 20% of the acceptor alcohol (allyl alcohol, glycerol, ethanol, ethylene glycol, and methanol, respectively). The products of these reactions included oligomeric alkyl beta-glycosides and reducing oligosaccharides. The high yield of alkyl beta-glycosides may be explained by the resistance of the xyloglucan beta-glycosides to cellulase-mediated hydrolysis. The resistance of the oligoxyloglucan beta-glycosides to endo glucanase catalyzed hydrolysis supports the hypothesis that productive binding of the glycan substrate depends on its interaction with enzyme subsites on both sides of the cleavage point, leading to distortion of the ring geometry of the residue whose glycosidic bond is cleaved. Oligoxyloglucan beta-glycosides were purified by a combination of gel-permeation and reversed-phase HPLC and were structurally characterized by MS and NMR spectroscopy. These results demonstrate that novel oligosaccharide beta-glycosides can be efficiently produced by enzyme-catalyzed fragmentation/transglycosylation reactions starting with a polysaccharide donor substrate. This class of reactions may represent a convenient source of beta-glycosides to be used as synthons for the rapid synthesis of complex glycans.
Alcohols↗
Variations in human urinary O-hydroxylysyl glycoside levels and their relationship to collagen metabolism.
Two O-hydroxylysyl glycosides, Hyl-Gal-Glc and Hyl-Gal, have been isolated from normal human urine and shown to be identical to two glycosides isolated from alkaline hydrolysates of collagen. A relatively sample and reproducible analytical procedure has been devised to measure the levels of these glycosides in human urine. By the use of this procedure it was shown that a normal diet has only a small effect on 24-hr urinary excretion levels of these glycosides indicating an endogenous origin. Urinary glycoside levels appear to be highest in children, roughly paralleling collagen turnover as indicated by urinary hydroxyproline levels. Collagen turnover equivalents calculated from urinary hydroxylysyl glycoside levels were found to be significantly larger than collagen turnover equivalents calculated from urinary hydroxyproline levels. This suggests that urinary glycosides are more quantitative indicators of collagen metabolism than urinary hydroxyproline. The ratio of Hyl-Gal-Glc to Hyl-Gal was measured in urines of diseased as well as normal individuals and a bimodal distribution was found. Alkaline hydrolysates of different human connective tissue collagens showed that only bone collagen, of the collagens examined, had a low ratio of Hyl-Gal-Glc to Hyl-Gal compared to human urine. Other collagens examined had higher ratios than found in human urine. On the basis of these results it is postulated that the bimodal distribution of glycoside ratios represents two populations of collagen turnover, the lower ratio population having a high bone collagen turnover, the lower ratio population having a high bone collagen turnover relative to the second population. Examination of the types of subjects making up the two populations supports this hypothesis. These data suggest that urinary O-hydroxylysyl glycoside excretion, in addition to providing a more quantitative estimate of collagen turnover than urinary hydroxyproline, may prove to be of value as a specific means of studying the metabolism of bone collagen.
Achondroplasia↗
Bioactive glycosides from Chinese medicines.
Glycosides are the bioactive components of many famous Chinese medicines. Here reported are some bioactive glycosides we discovered from Chinese medicines in recent years. (1) Phenolic glycosides from Chinese medicines: Gastrodia elata, Aconitum austroyunanense and Helicia erratica, three bioactive phenolic glycosides were discovered and two of them have been developed into new drugs. (2) Terpenoidal glycosides: a) Monoterpenoid: the sweroside from Swertia moleensis has been developed into an anti-hepatitis drug; b) Diterpenoid: Phlomis betonicoides contains sweet glycosides; c) Triterpenoid: many biologically active triterpenoid glycosides were isolated from Panax plants and Siraitia grosvenorii. (3) Steroidal glycosides: a) C21-steroid: Cynanchum otophyllum and C. atratrum contain anti-epilepsy and anti-tumor glycosides; b) C27-steroid Hemostatic saponins were found in Paris polyphylla.
Animals↗
Studies on cardioactive steroids. III. Characterization of different cardiac glycosides by their effects on contractility and rhythmicity at different extracellular potassium concentrations.
In the present paper, the naturally occurring glycosides digitoxin, gitoxin, 16-acetyl-gitoxin, digoxin, cymarol, ouabain, and proscillaridin, and the semi-synthetic 16-epi-gitoxin and 16-acetyl-16-epi-gitoxin are investigated as to their inotropic action and their effects on rhythmicity at isolated spontaneously beating atria of the guinea-pig heart in dependence on the variation of the potassium concentration of the nutritive fluid ([K+]0: 1.34, 2.68, and 5.36 mM resp.). The major results are as follows. 1. Effects of raising [K+]0 from 1.34 to 2.68 mM: The range of the inotropically effective concentrations as well as the size of the maximum inotropic action are more or less strongly improved with all glycosides. The glycoside concentrations required to get inotropic maximum had to be increased to a high degree with proscillaridin and digoxin. The mean arrhythmia percentage occurring at the inotropic maximum is either decreased (gitoxin, 16-epi-gitoxin, digoxin, proscillaridin), unchanged (digitoxin, 16-acetyl-16-epi-gitoxin) or even increased (16-acetyl-gitoxin, cymarol, ouabain). The inotropic value is improved to a high extent with gitoxin only. 2. Effect of raising [K+]0 from 2.68 to 5.36 mM: The range of the inotropically effective concentrations is extended (digitoxin and cymarol) or diminished (proscillaridin), but remains essentially unchanged with most glycosides. The size of the maximum inotropic effect is increased with digoxin, ouabain and 16-epi-gitoxin, but decreased significantly with digitoxin and proscillaridin. The glycoside concentrations required to produce the inotropic maximum are essentially unchanged with the exception of 16-epi-gitoxin, 16-acetyl-gitoxin and ouabain. The mean arrhythmia percentage at the maximum inotropic effect is dramatically reduced with digoxin, cymarol and proscillaridin. The inotropic value is improved with all glycosides except digitoxin. 3. Evaluation of the various glycosides: When judged on the basis of the range of inotropically effective concentrations, the maximum inotropic effect, the mean arrhythmia percentage at the inotropic maximum and the inotropic value, the best first three glycosides include 16-epi-gitoxin and digoxin. 16-Epi-gitoxin and its 16-acetate show that most favourable relationship between the effect on contractility and rhythmicity. The cause of the differential actions of the structurally-different glycosides on contractility and rhythmicity is hypothesized to be due to divergences in structure and/or conformation of the receptor areas of (Na+ + K+)-ATPase of contractile and excitable cells.
Animals↗
Biochemical and cross-resistance studies with HeLa cell mutants resistant to cardiac glycoside SC4453. Regulation of the resistant form of Na+/K+-ATPase in the mutant cells.
In HeLa cells, stable mutants which are between 25-to about 200-fold resistant to the cardiac glycoside derivative SC4453 (a digoxin analog which contains a pyridazine ring in place of a lactone ring in the C-17 position) have been isolated after a single step selection in the presence of the drug. Based on their cross-resistance pattern towards various cardiac glycosides, the mutants resistant to SC4453 (SCR mutants) appear to be of two different kinds and they differ from the two classes of ouabain-resistant mutants described previously (Gupta, R. S., and Chopra, A. (1985) J. Biol. Chem. 260, 6843-6850). One type of SCR mutants (designated as group C) exhibit a high degree of cross-resistance to all cardiac glycosides and their genins (viz. ouabain, digitoxin, digoxin, digoxigenin, convallatoxin, gitoxin, strophanthidin, and bufalin). In contrast, the second type of SCR mutant (group D) exhibit considerable resistance to only SC4453, digoxin, and digoxigenin, but showed very little or no cross-resistance to the other cardiac glycosides examined. The cross-resistance of the mutants towards cardiac glycosides was highly specific as they exhibited no cross-resistance towards a large number of other structurally and functionally related compounds (viz. ethacrynic acid, sanguinarine nitrate, penicillic acid, methyl quinolizinum bromide, 5,5'-diphenylhydantoin, deoxycorticosterone, vanadium pentoxide, and adriamycin). The cellular uptake of 86Rb in the mutant cells was found to be resistant to specific cardiac glycosides. Studies on the sensitivity of plasma membrane Na+/K+-ATPase to cardiac glycosides show that about 10-15% of the enzymic activity in the mutant cells was highly resistant to inhibition by the specific drugs to which the mutants exhibit increased resistance. Very interestingly, when the mutant cells are grown in cardiac glycoside-containing medium, the resistant form of the enzyme accounts for about 50-60% of the total enzyme. These results show that both classes of SCR mutants are affected in Na+/K+-ATPase and that the amount of the resistant enzyme in the mutant cells is regulated in response to cardiac glycosides.
Cardiac Glycosides↗