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PubMed1990

Platelet adhesion to collagen. Factors affecting Mg2(+)-dependent and bivalent-cation-independent adhesion.

Platelet adhesion to collagens immobilized on plastic has been measured, with the following results. (1) Human, but not rabbit, platelets adhered readily to pepsin-extracted monomeric collagens in an Mg2(+)-dependent manner. (2) Rabbit platelets adhered to a monomeric collagen extracted without pepsin by a process that was cation-independent; human platelet adhesion to this collagen exhibited a cation-independent element. (3) Human platelet adhesion to polymeric collagens, including intact native fibres and those reconstituted from pepsin-extracted monomeric collagens, exhibited appreciable cation-independence; adhesion of rabbit platelets to these collagens occurred only by a cation-independent process; pepsin treatment of the intact fibres caused a reduction in cation-independent binding. Two mechanisms of adhesion can therefore be distinguished, one Mg2(+)-dependent, expressed by human, but not rabbit, platelets, the other cation-independent and exhibited by platelets of both species. Mg2(+)-dependent and cation-independent adhesion sites are located within the triple helix of collagen, but the latter sites are only expressed in collagen in polymeric form. In neither case is the helical conformation of the sites essential for their binding activity. Cation-independent adhesion sites are also located in the pepsin-sensitive non-helical telopeptides of collagen and can be expressed in both monomeric and polymeric collagens. Chemical modification of collagen lysine residues indicates that specific lysine residues may be involved in Mg2(+)-dependent adhesion. Adhesion using human citrated platelet-rich plasma is Mg2(+)-independent. Plasma contains factors, conceivably the adhesive proteins fibronectin and von Willebrand factor, that promote the Mg2(+)-independent mechanism.

Animals↗
PubMed1997

Pulmonary surfactant inhibits cationic liposome-mediated gene delivery to respiratory epithelial cells in vitro.

Cationic lipid-mediated transfection of the alveolar epithelium in vivo will require exposure of plasmid DNA and cationic lipids to endogenous surfactant lipids and proteins in the alveolar space. Effects of pulmonary surfactant and of surfactant constituents on transfection in vitro of two respiratory epithelial cell lines (MLE-15 and H441) with a plasmid encoding the luciferase reporter gene were studied using two cationic lipid formulations: 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/cholesterol (DMRIE/C) and 1,2-dioleoyl-3-trimethylammonium propane/dioleoyl phosphatidylethanolamine (DOTAP/DOPE). Gene expression, as assessed by luciferase activity, decreased as increasing concentrations of natural surfactant were added to cationic lipid-DNA complexes. Incorporation of phospholipids DOPC/DOPG or surfactant proteins SP-B or SP-C in the cationic lipid formulation inhibited transfection. A fluorescent lipid mixing assay was used to determine the effects of surfactant proteins SP-B and SP-C on mixing between cationic lipid-DNA complexes and surfactant lipid vesicles. Mixing between DOPC/DOPG vesicles and cationic lipid-DNA complexes in the absence of added proteins amounted to 10-20%. Addition of SP-B or SP-C increased the mixing of DOPC/DOPG vesicles with DOTAP/DOPE-DNA complexes, but not DMRIEC-DNA complexes. These results demonstrate that pulmonary surfactant lipids and proteins inhibit transfection with cationic lipid-DNA complexes in vitro, and may therefore represent a barrier to gene transfer in the lung.

Animals↗
PubMed1978

Effect of cation content of agar on the activity of gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa.

Fifty-five strains of Pseudomonas aeruginosa were tested against arithmetic increments in concentrations of gentamicin, tobramycin, and amikacin in 14 different lots of Mueller-Hinton agar. The divalent cation content of each lot was determined by atomic absorption spectrometry. The relation between mean minimal inhibitory concentration (MIC) for strains within each lot and cation content was studied by stepwise regression. Among the cations, the content of Zn++ most highly correlated with the MIC of each aminoglycoside; however, Zn++ accounted for only 23%, 60%, and 47% of the variability in the mean MIC of gentamicin, tobramycin, and amikacin, respectively, against all strains. In two-cation models Zn++ with Ca++ or Cu++ was most highly correlated with the mean MICs of the three aminoglycosides against all strains. No divalent cation, either singly or in combination with one or two other cations, gave a good prediction of the MICs of the aminoglycosides in agar. Furthermore, there was variability in the cations that most highly correlated with the MICs for some strains. These observations support the concept that ionic strength, cations, and a variety of other as yet poorly defined components of media influence the activity of aminoglycosides against P. aeruginosa.

Agar↗
PubMed1992

Interactive effects of Al, h, and other cations on root elongation considered in terms of cell-surface electrical potential.

The rhizotoxicities of Al(3+) and of La(3+) to wheat (Triticum aestivum L.) were similarly ameliorated by cations in the following order of effectiveness: H(+) approximately C(3+) > C(2+) > C(1+). Among tested cations of a given charge, ameliorative effectiveness was similar except that Ca(2+) was slightly more effective than other divalent cations and H(+) was much more effective than other monovalent cations. H(+) rhizotoxicity was also ameliorated by cations in the order C(3+) > C(2+) > C(1+). These results suggest a role for cell-surface electrical potential in the rhizotoxicity of Al(3+), La(3+), H(+), and other toxic cations: negatively charged cell surfaces of the root accumulate the toxic cations, and amelioration is effected by treatments that reduce the negativity of the cell-surface electrical potential by charge screening or cation binding. Membrane-surface activities of free Al(3+) or La(3+) computed according to a Gouy-Chapman-Stern model correlated well with growth inhibition, which correlated only poorly with Al(3+) or La(3+) activities in the external medium. The similar responses of Al-intoxicated and La-intoxicated roots to ameliorative treatments provide evidence that Al(3+), rather than AlOH(2+) or Al(OH)(2) (+), is the principal toxic species of mononuclear Al. Comparisons of the responses of Al-sensitive and Al-tolerant wheats to Al(3+) and to La(3+) did not support the hypothesis that varietal sensitivity to Al(3+) is based upon differences in cell-surface electrical potential.

Journal Article↗
PubMed1981

Effect of monovalent cations on the aggregation of tobacco mosaic virus by chondroitin sulfate.

The mechanism of precipitation of tobacco mosaic virus by chondroitin sulfate in the presence of various monovalent cations was investigated kinetically by means of turbidimetry. The virus solution became turbid on the addition of chondroitin sulfate, and led to separation of the virus as a crystalline phase. In the presence of monovalent cations the degree of precipitation of the virus by chondroitin was reduced with the increase in monovalent cation concentration. The order of the reduction was Li+ less than Na+ less than K+, which is reversely analogous to the lyotropic series. The least hydrated cation, K+, reduced the degree of precipitation of tobacco mosaic virus the most because the radius of the sphere equivalent to chondroitin sulfate was diminished most strongly by K+ ion. The effect of the monovalent cations on the precipitation supports our assumption that the virus precipitation results from incompatibility and mutual spatial exclusion between the virus and chondroitin. The maximum turbidities, the initial slopes, and the aggregation half-time were measured by varying the monovalent cation concentrations. The former two parameters decreased with the increase in cation concentration, whereas the aggregation half-time increased. A lag time was present and the effect of the cations increased in the order K+ less than Na+ less than Li+.

Chemical Phenomena↗
PubMed1995

Long-lasting activation of cation current by low concentration of endothelin-1 in mouse fibroblasts and smooth muscle cells of rabbit aorta.

1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell recordings and monitoring the changes in intracellular free Ca2+ concentrations ([Ca2+]i) with a Ca2+ indicator, fluo-3. A similar type of coupling was investigated in freshly dispersed vascular smooth muscle cells (VSMCs) of rabbit thoracic aorta by use of whole-cell recordings. 2. In Ltk- cells expressing recombinant human ETA receptors, concentrations of ET-1 (10(-8) M, 10(-9) M) evoked an initial transient peak and a subsequent sustained elevation in [Ca2+]i whereas a lower concentration of ET-1 (10(-10) M) evoked only a sustained elevation of [Ca2+]i. After removal of extracellular Ca2+, ET-1 evoked only an initial peak without a sustained elevation of [Ca2+]i. The sustained elevation induced by 10(-10) M ET-1 was blocked by 300 microM mefenamic acid (a cation channel blocker) but not by 10 microM nifedipine (a blocker of voltage-operated Ca2+ channel). 3. In whole-cell recordings with Ltk- cells, a brief (3-5 min) application of ET-1 (10(-10) M) induced a sustained inward current at a holding potential of -60 mV. The current-voltage relationship revealed that the reversal potential of the ET-1-induced current was close to 0 mV (1.9 mV) and was not altered by reducing the concentration of Cl- in the bath solution, indicating that the current is carried by cations. The current was reversibly blocked by 300 microM mefenamic acid, and it persisted after all cations in the bath solution had been replaced by Ca2+ (5 or 30 mM) and nonpermeant cation N-methyl-D glucamine,indicating that the ET-1-activated channel is permeable to Ca2+. Activation of the current was independent of membrane potential and the current was induced even after addition of a high concentration (10 mM) of a Ca2+ chelator, EGTA, to the pipette solution.4. In whole-cell recordings from rabbit aortic VSMCs, ET-l (101-10 M) induced a sustained inward current at a holding potential of -60 mV. The reversal potential was - 12 mV and was not altered when the concentration of Cl- in the pipette solution was decreased, indicating that the current is carried by cations. Again activation of the current was independent of membrane potential and was observed even after addition of a high concentration (10 mM) of a Ca2+ chelator, EGTA to the pipette solution. The current was reversibly blocked by 300 microM mefenamic acid and was permeable to Ca2+,showing marked similarities to ET-1-induced cationic current in Ltk- cells.5. These results indicate that in Ltk- cells transfected with cDNA for recombinant ETA receptors andVSMCs, ETA receptors can functionally couple with a nonselective cation channel permeable to Ca2+.Thus the present data suggest that the cation channel plays an essential role in the sustained elevation of[Ca2+]i at low concentrations of ET-l by causing Ca2+ entry through the channel.

Aniline Compounds↗
PubMed1981

Interactions of cations with membrane fractions of smooth and rough strains of Salmonella typhimurium and other Gram-negative bacteria.

Addition of cations (20 to 50 mM for Mg(2+) or Ca(2+) or 100 to 500 mM for Na(+)) to N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer during preparation of membranes from smooth and rough strains of Salmonella typhimurium LT2, Salmonella minnesota, and Escherichia coli O8 had two effects on the composition of the membranes isolated. First, in rough strains of chemotypes Ra to Re the "total membranes" (pellets from high-speed centrifugation) were deficient in the proteins of the outer membrane. The missing proteins were found to have been sedimented in a prior low-speed centrifugation in a fraction we call "cation-aggregated membranes." Since these membranes were enriched for lipopolysaccharide and for outer membrane proteins, deficient in succinic dehydrogenase, and contained primarily the dense peak after sucrose gradient centrifugation, it appears to be relatively pure outer membrane. About 10% of the membrane protein of smooth strains and up to 50% that of rough strains were cation-aggregated membranes, appearing to contain most of the outer membrane of rough strains. Thus, cation aggregation may be a useful means of preparation of outer membrane samples. The second effect was that with cation addition, several high-molecular-weight proteins not seen when membranes were prepared without cation addition were found in the total membranes of both smooth and rough strains after high-speed centrifugation. These proteins were bound by cations to the inner membranes, since they were soluble in Triton X-100 and separated into the less dense peak upon sucrose gradient centrifugation. They originated from the cytoplasm or the periplasm, since they corresponded to soluble proteins found in the supernatant after high-speed centrifugation and were depleted from this supernatant when preparation was done in the presence of cations.

Bacterial Proteins↗
PubMed1979

Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay.

A specific radioimmunoassay has been developed for human pancreatic cationic trypsin. The assay has been employed for the determination of immunoreactive forms of pancreatic cationic trypsin in blood. The trypsin employed as radioiodinated tracer in the assay was inactivated with tosyl-L-lysine chloromethyl ketone (TLCK) to prevent binding of the tracer to the serum inhibitors while maintaining its immunoreactivity. The average normal serum level determined was 26 ng/ml, with a range of 12--41 ng/ml. Eight of nine patients with acute pancreatic inflammation had at least a 15-fold elevation of total serum immunoreactive cationic trypsin. Cationic trypsinogen and cationic trypsin bound to alpha1-antitrypsin cross-react strongly in the radioimmunoassay. Thus it is possible to measure these potential molecular forms of cationic trypsin in serum. When normal human serum was fractionated on Sephadex G-200, all of the immunoreactive material eluted as a single peak of approximately 23,000 mol wt. No cationic trypsin could be detected in association with alpha1-antitrypsin or alpha2-macroglobulin. The 23,000-mol-wt peak was definitively shown to contain trypsinogen by affinity chromatography and by activation with human enteropeptidase. The identification of cationic trypsinogen in blood implies that the zymogen is secreted into the circulation by the pancreas rather than entering the bloodstream via absorption from the intestine.

Enteropeptidase↗
PubMed1998

Cationic polymer and lipids enhance adenovirus-mediated gene transfer to rabbit carotid artery.

BACKGROUND AND PURPOSE: Improvement of efficiency of gene transfer to endothelium could be useful for several applications. We tested the hypothesis that cationic nonviral molecules augment adenovirus-mediated gene transfer to blood vessels, perhaps by alteration of the surface charge of adenovirus and facilitation of binding to endothelium. METHODS: Carotid arteries from rabbits were incubated in vitro for 0.5 to 2 hours with an adenoviral vector alone or noncovalent complexes of adenovirus with poly-L-lysine (a cationic polymer) or lipofectin (a cationic lipid). Binding of adenovirus to the vessels was evaluated immediately after incubation with virus, and assay of transgene (ss-galactosidase) activity and histochemistry were performed 24 hours after gene transfer. To determine whether cationic molecules can be used to augment alteration of vascular function by adenovirus-mediated gene transfer, we also examined effects on gene transfer of endothelial nitric oxide synthase. RESULTS: Assay of ss-galactosidase activity indicated that both cationic molecules increased transgene expression in vessels by approximately 5- to 6-fold. In contrast, when endothelium was removed from the vessels after gene transfer, poly-L-lysine and lipofectin did not significantly increase transgene activity. Histochemistry for ss-galactosidase also suggested that the adenovirus-cationic molecule complexes augmented transgene expression mainly in the endothelium. In addition, we found that complexing adenovirus with cationic molecules increased binding of adenovirus to the vessels. After gene transfer with recombinant adenovirus containing endothelial nitric oxide synthase, calcium ionophore (A23187) produced greater relaxation of vessels treated with adenovirus complexed with poly-L-lysine or lipofectin than those treated with adenovirus alone. CONCLUSIONS: Cationic molecules improve the efficiency of adenovirus-mediated gene transfer to blood vessels.

Adenoviridae↗
PubMed1991

Role of magnesium in the dietary cation-anion balance equation for ruminants.

Eight midlactation Holstein cows (four primiparous) were assigned to replicated 4 x 4 Latin squares with a 2 x 2 factorial arrangement of treatments. The basal diet was formulated to contain 0 milliequivalents (Na + K) - Cl/100 g of diet DM. Treatment diets of high and low dietary cation-anion balance were achieved by adding appropriate amounts of supplemental Na + K (added on an equivalent basis) or Mg to the basal diet. Milk and protein yield were increased as well as DMI and FCM for Na + K diets The high concentration of cation increased milk fat percentage. The cation-anion balance (using Mg as a cation) had no effect on any of the production parameters observed. The higher cation-anion balances increased blood bicarbonate levels and plasma Na. Urinary Ca excretion was increased for the Mg diets. Urinary pH increased with both the source of cation (Na + K) and the concentration of cation (high) in the diet. other minerals were unaffected in milk, plasma, or urine. Responses measured in this trial reflect treatments calculated using the equation milliequivalents (Na + K) - Cl/100 g diet DM or (Na + K) - (Cl + S)/100 g diet DM, suggesting that Mg plays a minor role in dietary cation-anion balance.

Animal Feed↗
PubMed1991

Effects of copper sources and dietary cation-anion balance on copper availability and acid-base status in dairy calves.

Twenty-four Holstein and Jersey calves (14 Holstein), 4 to 11 d of age, were assigned randomly to six treatments in a 2 x 3 factorial arrangement to examine the effects of Cu sources and dietary cation-anion balance on Cu availability and acid-base balance. Treatments were cationic basal diet (20 meq of dietary cation-anion balance on a DM basis), cationic basal diet supplemented with CuO, cationic basal diet supplemented with CuSO4, anionic basal diet (-10 meq), anionic basal diet supplemented with CuO, and anionic basal diet supplemented with CuSO4. Copper sources did not show any effect on growth of calves. The cationic diet increased calf growth compared with the anionic diet at wk 12 of the experiment. Blood pH was increased by the cationic diet in comparison with the anionic diet at wk 8 and 12. Blood pH also was increased by CuSO4 compared with CuO treatment in the early period of the treatment. Blood bicarbonate concentration was decreased by CuO and the anionic diet. Interactions between Cu sources and cation-anion balance were found for blood pH and bicarbonate concentration. Liver Cu concentration was increased by CuSO4 but not by CuO supplementation compared with control. Therefore, CuSO4 was found to be highly available, whereas CuO was a very poorly available source of Cu for young calves.

Acid-Base Equilibrium↗
PubMed1991

Effects of manipulating dietary cation-anion balance on macromineral balance in sheep.

Effect on macromineral balance in sheep of dietary excess of inorganic anions (Cl and S) or inorganic cations (Na and K) was studied. Dietary cation-anion balance was calculated as milliequivalents [(Na + K) - (Cl + S)] kg-1 of DM. Eight crossbred wethers were fed two levels of Ca, designated high Ca (.82%) or normal Ca (.48%), with four treatment each, three of which differed in dietary cation-anion balance. Control and two treatments had +284, +61, and -27 meq kg-1 of DM for high Ca and +343, +218, and +63 meq kg-1 of DM for normal Ca, respectively. A fourth treatment was control plus injection of vitamin D3 (16,670 IU kg-1 of BW). Reducing dietary cation-anion balance reduced Ca retention by increasing excretion of urinary Ca. Apparent absorption of Ca was similar across cation-anion balances. There was no correlation observed between dietary cation-anion balance and concentration of plasma Ca. No difference was observed in apparent absorption of Ca between high and normal Ca. This result may be related to an oversupply of dietary Ca. Magnesium retention as a proportion of that absorbed for lowest cation-anion balance was smaller than that for the intermediate balance and control plus vitamin D3, although not different from control. Results showed that reduced dietary cation-anion balance resulted in a reduction of Ca retention.

Analysis of Variance↗
PubMed1995

Acid-base status, renal function, water, and macromineral metabolism of dry cows fed diets differing in cation-anion difference.

Dietary cation-anion difference was defined as the summation of the milliequivalents of Na and K minus the sum of the milliequivalents of Cl and S per kilogram of DM. Twelve Holstein cows were used in a crossover experiment to compare the effects of changing the cation-anion difference of a diet based on haylage. Two cation-anion differences, 481.8 and 327.2 meq/kg, were compared. Increased dietary cation-anion difference had no significant effects on BW or intake and digestibility of DM, ADF, NDF, and N. The diet with a cation-anion difference of 481 meq/kg of DM increased apparent absorption of water and urine volume. Fecal excretion of Na and absorption and urinary excretion of S were increased by a cation-anion difference of 327 meq/kg of DM. Although blood concentrations were unaffected, lower dietary cation-anion difference reduced concentrations of H+ and HCO3- in urine and total urinary excretion of HCO3-. Plasma volume, packed cell volume, glomerular filtration rate, and effective renal plasma flow were unaffected by diet. Small changes in dietary cation-anion differences, even within the positive range, affected acid-base status and water metabolism of dry pregnant cows without affecting renal function or blood volume.

Absorption↗
PubMed1992

Eosinophil granule cationic proteins regulate complement. I. Activity on the alternative pathway.

Eosinophil granules contain several cationic proteins that mediate tissue damage in allergic disease. The present study examined the capacity and mechanisms by which these cationic proteins regulate activity of the alternative pathway of C. Eosinophil peroxidase and eosinophil cationic protein inhibited formation of cell-bound alternative pathway C3 convertase, causing 50% inhibition of lysis at about 0.19 and 0.75 microgram/10(7) cellular intermediates, respectively. Major basic protein inhibited alternative pathway C3 activity by only 19% at 1.5 micrograms/10(7) cellular intermediates. Eosinophil-derived neurotoxin had no activity on the alternative pathway. The eosinophil granule proteins were examined for the mechanism by which they inhibited alternative pathway activity. Eosinophil peroxidase and major basic protein inhibited fluid phase factor B consumption in a reaction mixture that also contained factors D and C3b, eosinophil-derived neurotoxin had no activity on factor B consumption, and eosinophil cationic protein consumed factor B in the absence of C3b and factor D. Both eosinophil cationic protein and eosinophil peroxidase enhanced the decay of preformed alternative pathway convertase. Lysis of EAC4b,3b cellular intermediates formed to contain a low surface amount of C3b was more inhibited than was lysis of cells formed with a standard amount of C3b on the surface. This suggests that these eosinophil proteins acted predominantly on C3b to regulate alternative pathway activity. We also found that none of the eosinophil granule cationic proteins had any effect on later events after the formation of the C3 convertase. We conclude that although eosinophil-derived neurotoxin (isoelectric pH value (pI) = 8.9) does not regulate alternative pathway activity, the more highly charged eosinophil granule cationic proteins--major basic protein (pI = 10.9), eosinophil cationic protein (pI = 10.8), and eosinophil peroxidase (pI = 10.8)--do share the capacity to regulate C activity and may exert this activity in vivo.

Blood Proteins↗
PubMed1990

Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector.

The present investigations evaluated the effects in rats of repetitive administration of cationized rat albumin over an 8-week period with the future aim of using this modified protein as a vector to transport drugs across the brain capillary endothelial wall, i.e., the blood-brain barrier. Rat albumin was cationized at pH = 7.8 with hexamethylenediamine, and the isoelectric point of the protein was raised from 5.5 to approximately 8. The cationized protein was monomeric based on mobility during sodium dodecylsulfate polyacrylamide gel electrophoresis. After radiolabeling, the cationized rat serum albumin (RSA) was taken up by isolated rat or bovine brain microvessels, whereas radio-labeled native RSA was not taken up by the capillaries in vitro. The brain volume of distribution of the 3H-cationized RSA increased linearly over a 5-hr period after an intravenous injection of the isotope and reached a value of 46 +/- 3 microliter/g (mean +/- S.E.) by 5 hr, whereas the brain volume of distribution of the 125I-native RSA was constant during the 5-hr time period (9.3 +/- 0.7 microliter/g, which is equal to the brain blood volume). The cationized and native RSAs were administered daily (Monday through Friday) at a dose of 1 mg/kg subcutaneously to groups of rats for 4- and 8-week periods. This dosage regimen resulted in no discernible toxicity, based on the findings of normal weight gain, normal tissue histology and normal serum chemistry. Therefore, cationized rat albumin may be used in future studies that use the repetitive administration of cationized rat albumin chimeric peptides for the evaluation of the transport of these substances through the blood-brain barrier in vivo.

Animals↗
PubMed1987

Studies on the mechanism of passive cation fluxes activated by deoxygenation of sickle cells.

Sickle cells exhibit a striking increase in monovalent cation content upon deoxygenation. These deoxy cation fluxes are reversible upon reoxygenation, balanced (Na flux = K flux), activated under physiologic conditions of pH and PO2, and insensitive to ouabain and furosemide. Our recent evidence indicates that deoxy cation fluxes and the Na/K pump, acting in concert, contribute to cation depletion in sickle cells in vitro. The resultant dehydration worsens their rigidity and increases their tendency to sickle upon deoxygenation. Here we report our finding that deoxy cation fluxes are inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). This irreversible inhibitor of anion transport was effective at concentrations less than 1 microM. The reversible, competitive inhibitor, 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) also blocked deoxy cation fluxes, at 100 microM. Niflumic acid, which exhibits non-competitive inhibitory kinetics against anion transport, also inhibited deoxy cation fluxes at 50 microM. Phloretin (a non-competitive anion transport inhibitor), however, had no effect on deoxy fluxes. On the basis of these data, we propose the working hypothesis that deoxygenation of sickle cells causes a conformational change in the anion exchange protein which allows for the passage of cations and alters its sensitivity to inhibitors.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Influence of monovalent cations on the ultraviolet-visible spectrum of tryptophan tryptophylquinone-containing methylamine dehydrogenase from bacterium W3A1.

The influence of the monovalent cations on the UV-visible spectra of the methylamine dehydrogenase (MADH) from bacterium W3A1 was investigated. The spectra for the oxidized and 1- and 2-electron-reduced forms, unperturbed by bound cations, were obtained for the enzyme, and the extinction coefficients for these forms were determined. The binding of the following cations was investigated: Li+, Na+, K+, Rb+, Cs+, NH4+, (CH3)3NH+, and (CH3)4N+. It was shown that each cation produced unique spectral changes, some of which were pH-dependent. Except for NH4+, all spectral changes produced by binding of the monovalent cations can be explained by assuming two different binding sites in MADH (type I and type II sites). Na+ and K+ displayed monophasic binding to the type II site, (CH3)3NH+ and (CH3)4N+ displayed monophasic binding to the type I site, and Li+, Rb+, and Cs+ displayed either monophasic or biphasic binding to one or both sites depending on pH. The pH dependence for binding to the two sites is different, i.e. plots of log(Kd) versus pH have negative slopes approximately 1 for the type II site, whereas the negative slope is significantly less than 1 (0.6-0.8) for the type I site. This difference leads to pH-dependent changes in spectral features produced by binding of Li+, Rb+, and Cs+. The spectral changes seen during titrations with NH+4 were unlike those seen for any other cation. The binding of NH+4 was biphasic, and the spectra produced in each phase were unaffected by pH. It is assumed that this cation binds to the tryptophan tryptophylquinone cofactor to produce the iminoquinone in the first phase and then binds to the type I monovalent cation binding site in the second phase. It is suggested that binding of NH+4 (and CH3NH+3) to the type I site is a prelude to binding to the cofactor.

Bacteria↗
PubMed1998

Heterologous expression of various P-glycoproteins in polarized epithelial cells induces directional transport of small (type 1) and bulky (type 2) cationic drugs.

We recently showed that absence of mdr1-type P-glycoprotein (P-gp) in mice resulted in profoundly reduced hepatic and intestinal clearance of type 1 and type 2 cationic drugs compared with that in wild-type mice. These data strongly support the concept that mdr1-type P-gps are involved in the disposition of cationic amphiphilic drugs from the body. We tested the hypothesis that mdr1-type P-gps are involved in the transmembrane transport of organic cations in epithelial cells expressing various drug-transporting P-gps. Therefore, transepithelial transport of the P-gp substrate vinblastine, the steroidal (type 2) cation vecuronium, the relatively small (type 1) cationic compound azidoprocainamide methoiodide and the aliphatic cation tri-n-butylmethylammonium were measured. Apical expression of the mdr1a, mdr1b or MDR1 gene in confluently grown polarized transformed LLC-PK1 cells resulted in highly enhanced apical directed secretion of all the drugs tested compared with controls. The vectorial transport of tri-n-butylmethylammonium in the apical direction in the P-gp (over)expressing cells could be inhibited by vinblastine. The present observations show that apical secretion of type 1 as well as of type 2 organic cations is enhanced significantly in the presence of apical expressed mdr1-type P-gp. These findings provide evidence for the involvement of drug-transporting P-gp in transmembrane transport of various organic cations, including relatively small molecular weight aromatic and aliphatic compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗