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At least 469 records · Page 26Linked to original sources
PubMed1998

Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in which both mdr1a and mdr1b genes have been disrupted.

1. We have used mice with homozygously disrupted mdr1a and mdr1b genes (mdr1a/1b (-/-) mice) to study the role of the mdr1-type P-glycoprotein (P-gp) in the elimination of cationic amphiphilic compounds from the body. These mice lack drug-transporting P-gps, but show no physiological abnormalities under laboratory conditions and have normal bile flow. 2. 3H-labelled cationic drugs were administered intravenously (i.v.) to mice as a single bolus dose and the disposition of the studied cationic drugs was investigated by focusing on drug secretion into bile, intestinal lumen and urine. 3. Hepatobiliary secretion of the investigated cationic drugs was profoundly reduced in mice devoid of the mdr1-type P-gps. In fact, the cumulative biliary output, measured during 1 h, of the small type 1 compounds tri-butylmethyl ammonium (TBuMA) and azidoprocainamide methoiodide (APM), as well as of the more bulky type 2 cationic drug vecuronium, was reduced by at least 70% in the mdrla/lb (-/-) mice compared to wild-type. 4. The intestinal secretion of TBuMA, APM and vecuronium was also profoundly reduced in mdrla/lb (-/-) mice compared to wild-type mice. The absence of the mdrl-type P-gp resulted in virtual elimination of intestinal secretion of TBuMA and APM (>90% reduced as compared to wild-type (P=0.0001 and 0.0022, respectively)). The intestinal secretion of the type 2 cation drug vecuronium was reduced by 58% (P=0.0004) compared to the wild-type mice. 5. Increased renal clearances of both the type 1 compounds TBuMA and APM and also of the type 2 cationic compound vecuronium in the mdrla/lb (-/-) mice were observed. Furthermore, the balance between hepatic, intestinal and renal clearances of small type 1 organic cations clearly shifted towards a predominant role for renal clearance. Increased renal clearance may be explained by (over)expression of additional mechanisms for renal organic cation secretion, alternatively they may also point to an as yet undefined role of P-glycoprotein in kidney physiology and renal secretory function. 6. We conclude that the elimination from the body of a broad spectrum of cationic amphiphilic drugs via liver and intestine, is largely dictated by the activity of mdrl-type P-glycoproteins.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1989

Blood-brain barrier transport of cationized immunoglobulin G: enhanced delivery compared to native protein.

IgG molecules are potential neuropharmaceuticals that may be used for therapeutic or diagnostic purposes. However, IgG molecules are excluded from entering brain, owing to a lack of transport of these plasma proteins through the brain capillary wall, or blood-brain barrier (BBB). The possibility of enhanced IgG delivery through the BBB by cationization of the proteins was explored in the present studies. Native bovine IgG molecules were cationized by covalent coupling of hexamethylenediamine and the isoelectric point was raised to greater than 10.7 based on isoelectric focusing studies. Native and cationized IgG molecules were radiolabeled with 125I and chloramine T. Cationized IgG, but not native IgG, was rapidly taken up by isolated bovine brain microvessels, which were used as an in vitro model system of the BBB. Cationized IgG binding was time and temperature dependent and was saturated by increasing concentrations of unlabeled cationized IgG (dissociation constant of the high-affinity binding site, 0.90 +/- 0.37 microM; Bmax, 1.4 +/- 0.4 nmol per mg of protein). In vivo studies documented enhanced brain uptake of 125I-labeled cationized IgG relative to [3H]albumin, and complete transcytosis of the 125I-labeled cationized IgG molecule through the BBB and into brain parenchyma was demonstrated by thaw-mount autoradiography of frozen sections of rat brain obtained after carotid arterial infusions of 125I-labeled cationized IgG. These studies demonstrate that cationization of IgG molecules greatly facilitates the transport of these plasma proteins through the BBB in vivo, and this process may provide a new strategy for IgG delivery through the BBB.

Animals↗
PubMed1999

The integral divalent cation within the intermolecular purine*purine. pyrimidine structure: a variable determinant of the potential for and characteristics of the triple helical association.

In vitro assembly of an intermolecular purine*purine.pyrimidine triple helix requires the presence of a divalent cation. The relationships between cation coordination and triplex assembly were investigated, and we have obtained new evidence for at least three functionally distinct potential modes of divalent cation coordination. (i) The positive influence of the divalent cation on the affinity of the third strand for its specific target correlates with affinity of the cation for coordination to phosphate. (ii) Once assembled, the integrity of the triple helical structure remains dependent upon its divalent cation component. A mode of heterocyclic coordination/chelation is favorable to triplex formation by decreasing the relative tendency for efflux of integral cations from within the triple helical structure. (iii) There is also a detrimental mode of base coordination through which a divalent cation may actively antagonize triplex assembly, even in the presence of other supportive divalent cations. These results demonstrate the considerable impact of the cationic component, and suggest ways in which the triple helical association might be positively or negatively modulated.

Base Pairing↗
PubMed1987

Transmembrane cation movements during infection of Lactobacillus lactis by bacteriophage LL-H.

Phage LL-H-induced cation (K+, Na+, Mg2+, Ca2+, Cd2+) movements in Lactobacillus lactis bacteria have been studied. The effects of the m.o.i. and external cation concentration have been quantified. LL-H-induced effluxes showed cation specificity: K+ but practically no Mg2+ was lost during LL-H infection at low and moderate m.o.i. (up to about 100). Simultaneously to K+ efflux, divalent cation influxes were observed. These were dependent on the m.o.i. and on concentrations of external divalent cations and were concomitant with phage DNA transport, as concluded from the timing of the first phage-promoted biochemical changes in host cell metabolism and from electron microscopical observations. Host energy was not mobilized with phage-induced divalent cation influx. Several features of divalent cation influxes support the view that divalent cations have to be cotransported into the cell as counterions of LL-H DNA. Phage DNA associated with divalent cations may be the basic feature of the divalent cation dependence of LL-H infection.

Adenosine Triphosphate↗
PubMed1992

Extracellular divalent and trivalent cation effects on sodium current kinetics in single canine cardiac Purkinje cells.

1. The effects of the extracellular divalent cations barium, calcium, cadmium, cobalt, magnesium, manganese, nickel and zinc and the trivalent cation lanthanum on macroscopic sodium current (INa) were characterized in enzymatically isolated single canine cardiac Purkinje cells under voltage clamp at 9-14 degrees C. 2. All di(tri)valent cations produced depolarizing shifts in the conductance-voltage relationship. The order of efficacy, taken as the concentration required to produce a 5 mV shift in the mid-point of peak INa conductance, from least to most effective was (mM): Ca2+ (2.97) approximately Mg2+ (2.67) approximately Ba2+ (1.93) > CO2+ (1.02) approximately Mn2+ (0.88) > Ni2+ (0.54) > La3+ (0.095) approximately Cd2+ (0.083) approximately Zn2+ (0.076). 3. Addition of di(tri)valent cations also produced depolarizing shifts in voltage-dependent availability. The order of efficacy from the least to most effective was (mM): Cd2+ (7.70) approximately Mg2+ (6.86) approximately Ba2+ (4.50) > Ca2+ (2.47) approximately CO2+ (1.87) approximately Mn2+ (1.24) approximately Ni2+ (1.20) > Zn2+ (0.300) > La3+ (0.060). 4. The Gouy-Chapman-Stern equations were used to evaluate di(tri)valent cation efficacy in binding to surface charges. Surface charge density was estimated as 0.72 sites nm-2, and it was assumed that Mg2+, the divalent cation that produced the smallest shift, screened but did not bind to surface charges. Based on voltage-dependent availability, KD from lowest to highest affinity were (mM): Ba2+ (2500) > CO2+ (1670) approximately Mn2+ (1430) approximately Ca2+ = Cd2+ = Ni2+ (1200) > Zn2+ (250) > La3+ (30). 5. All di(tri)valent cations also produced a concentration-dependent acceleration of INa tail current relaxation. The addition of Ca2+ and La3+ produced acceleration of tail current relaxations that could be accounted for by the surface charge effects predicted from the shift in voltage-dependent availability. Cd2+, which produced almost no change in voltage-dependent availability, dramatically accelerated tail current relaxation. Zn2+, Ni2+, Mn2+ and CO2+ also produced greater acceleration of tail current relaxation than could be accounted for by surface charge effects. 6. Di(tri)valent cations delayed time to peak INa in a concentration-dependent manner. The time to peak INa-voltage relationship was well described by an exponential plus a constant, and di(tri)valent cations did not affect the slope factor or constant but shifted the relationship in the depolarizing direction. Similar to their effect on tail currents, addition of some di(tri)valent cations produced larger effects on time to peak INa than expected from the shift of voltage-dependent availability.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

In vitro transfection of plasmid DNA by cationized gelatin prepared from different amine compounds.

The objective of this paper is to compare the in vitro transfection efficiency of a luciferase plasmid DNA using cationized gelatin prepared from different amine compounds. The compounds used here were ethylenediamine, putrescine, spermidine and spermine, chemically introduced to the carboxyl group of gelatin for the cationization. Complexation of the cationized gelatin with the plasmid DNA was performed by simply mixing the two materials at various N+/P- mixing ratios (the molar number ratio of amino groups of gelatin to the phosphate groups of DNA) in aqueous solution. Gel retardation studies revealed that the formation of cationized-gelatin-plasmid DNA complexes depended on the N+/P- mixing ratio. The stronger interaction of plasmid DNA with the cationized gelatin of spermine compared to the other cationized gelatins was observed by an ethidium bromide intercalation assay and Scatchard binding analysis. When the transfection efficiency of plasmid DNA complexed with the various cationized gelatins at different N+/P- mixing ratios was evaluated for mouse L929 fibroblasts, the highest transfection efficiency was observed for the complex prepared from the cationized gelatin of spermine at a N+/P- mixing ratio of 2. The present study indicates that there is an optimal N+/P- mixing ratio and a type of amine compound or cationization extent of cationized gelatin to enhance the transfection efficiency of plasmid DNA.

Amines↗
PubMed1994

Crystal structures of synthetic 7 angstrom and 10 angstrom manganates substituted by mono- and divalent cations.

The crystal structures of synthetic 7 angstrom and 10 angstrom manganates, synthetic birnessite and buserite, substituted by mono- and divalent cations were investigated by X-ray and electron diffractions. The monoclinic unit cell parameters of the subcell of lithium 7 angstrom manganate, which is one of the best ordered manganates, were obtained by computing the X-ray powder diffraction data: a = 5.152 angstroms, b = 2.845 angstroms, c = 7.196 angstroms, beta = 103.08 degrees. On the basis of the indices obtained by computing the X-ray diffraction data of Li 7 angstrom manganate, monovalent Na, K and Cs and divalent Be, Sr and Ba 7 angstrom manganates were interpreted as the same monoclinic structure with beta = 100-103 degrees as that of Li 7 angstrom manganate, from their X-ray diffraction data. In addition, divalent Mg, Ca and Ni 10 angstrom manganates were also interpreted as the same monoclinic crystal system with beta=90-94 degrees. The unit cell parameters, especially a, c and beta change possibly with the type of substituent cation probably because of the different ionic radius, hydration energy and molar ratio of substituent cation to manganese. However, these diffraction data, except for those of Sr and Ba 7 angstrom and Ca and Ni 10 angstrom manganates, reveal only some parts of the host manganese structure with the edge-shared [MnO6] octahedral layer. On the other hand, one of the superlattice reflections observed in the electron diffractions was found in the X-ray diffraction lines for heavier divalent cations Sr and Ba 7 angstrom and Ca and Ni 10 angtrom manganates. The reflection presumably results from the substituent cation position in the interlayer which is associated with the vacancies in the edge-shared [MnO6] layer and indicates that the essential vacancies are linearly arranged parallel to the b-axis. Furthermore, the characteristic superlattice reflection patterns for several cations, Li, Mg, Ca, Sr, Ba and Ni, manganates were interpreted that the substituent cations are regularly distributed in the interlayer according to the exchange percentage of substituent cation to Na+. In contrast, the streaking in the a-direction observed strongly in the electron diffractions for heavier monovalent cations, K and Cs, manganates probably results from the disordering of their cations in the a-direction in the interlayer.

Cations↗
PubMed2003

Calcyclin mediates serum response element (SRE) activation by an osteoblastic extracellular cation-sensing mechanism.

UNLABELLED: The molecular mechanism of sensing extracellular cations in osteoblasts is controversial. Using an expression-cloning strategy, the calcium-binding protein calcyclin was found to mediate the response of MC3T3-E1 osteoblasts to extracellular cations, but not the calcimimetic NPS-568, indicating the presence of another cation-sensing mechanism. Further understanding of calcyclin function in osteoblasts may identify novel targets for regulating bone formation. INTRODUCTION: Extracellular calcium and other cations seem to regulate the function of osteoblasts through a distinct calcium-sensing mechanism that is coupled to activation of c-fos gene transcription. The identity of this calcium-sensing mechanism is unknown. METHODS: To identify molecules that participate in this extracellular cation-sensing pathway, we developed an expression cloning strategy in COS-7 cells using cation stimulation of a serum response element (SRE) luciferase reporter derived from the c-fos promoter to screen a mouse MC3T3-E1 osteoblast cDNA library. RESULTS AND CONCLUSIONS: We identified calcyclin (S100A6), a calcium-binding protein of the EF-hand type belonging to the S100 family, as being responsible for transferring a cation-sensing response from osteoblasts to COS-7 cells. Transfection of the calcyclin cDNA into COS-7 and HEK-293 cells confirmed that the overexpression of calcylin caused these cells to gain the ability to sense extracellular cations, including aluminum, gadolinium, calcium, and magnesium. Conversely, we found that an antisense calcyclin construct reduced calcyclin expression and partially inhibited the cation-sensing response in MC3T3-E1 osteoblasts. These results implicate calcyclin in the activation of SRE and establish a role for calcyclin as an accessory protein involved in the cation-sensing pathway in osteoblasts.

Amino Acid Sequence↗
PubMed2004

DOTAP (and other cationic lipids): chemistry, biophysics, and transfection.

Cationic lipid-mediated nucleic acid and protein delivery is becoming increasingly popular for in vitro and in vivo applications. While the chemistry of cationic lipid carriers is moving very rapidly, and more and more sophisticated molecules are being developed, it is worthwhile to look back to understand what has been achieved in the field of cationic lipids and why in some cases delivery based on cationic lipids works and in other cases it does not. For this purpose, DOTAP is one of the best candidates; it is the most widely used cationic lipid, it is relatively cheap, and it is efficient in both in vitro and in vivo applications. The vast amount of data that have accumulated on DOTAP and related molecules could provide invaluable clues to biophysical, structural, and biological mechanisms of transfection by cationic lipids. While many issues of cationic lipid transfection still remain unclear, this review will attempt to address mainly the following issues: (1) interplay of physicochemical parameters of DOTAP formulations; (2) impact of physicochemical parameters on transfection (lipofection) efficiency by cationic reagents, in vitro and in vivo; (3) structure-activity relationships of cationic lipid formulations in cell culture and in the living organism. In addition, in vivo applications of cationic lipids are reviewed, and the problems of local versus systemic administration of lipoplexes are discussed.

Animals↗
PubMedDate not supplied

Cation-pi bonding: a new perspective on the sorption of polycyclic aromatic hydrocarbons to mineral surfaces.

Recent molecular modeling and spectroscopic studies have suggested that relatively strong interactions can occur between aromatic pi donors and metal cations in aqueous solutions. The objective of this study was to characterize potential cation-pi interactions between pi donors and exchangeable cations accumulated at mineral surfaces via both spectroscopic and batch sorption methods. Quadrupolar splitting in deuterium nuclear magnetic resonance ((2)H NMR) spectroscopy for d(2)-dichloromethane, d(6)-benzene, and d(8)-toluene (C(6)D(5)- moiety) in aqueous suspensions of a Na-saturated reference montmorillonite unambiguously indicated the ordering of solute molecules with respect to the clay surface. The half line broadening (Delta nu(1/2)) of (2)H NMR of d(6)-benzene in montmorillonite suspensions showed that soft exchangeable cations generally resulted in more benzene sorption compared with harder cations (e.g., Ag(+) > Cs(+) > Na(+) > Mg(2+), Ba(2+)). In batch sorption experiments, saturating minerals (e.g., porous silica gels, kaolinite, vermiculite, montmorillonite) with a soft transition metal or softer base cations generally increased the polycyclic aromatic hydrocarbon (PAH) sorption relative to harder cations (e.g., Ag(+) >> Cs(+) > K(+) > Na(+); Ba(2+) > Mg(2+)). Sorption of phenanthrene to Ag(+)-saturated montmorillonite was much stronger compared with 1,2,4,5-tetrachlorobenzene, a coplanar non-pi donor having slightly higher hydrophobicity. In addition, a strong positive correlation was found between the cation-dependent sorption and surface charge density of the minerals (e.g., vermiculite, montmorillonite >> silica gels, kaolinite). These results, coupled with the observations in (2)H NMR experiments with montmorillonite, strongly suggest that cation-pi bonding forms between PAHs and exchangeable cations at mineral surfaces and affects PAH sorption to hydrated mineral surfaces.

Adsorption↗
PubMed1998

Structural requirements for cationic lipid mediated phosphorothioate oligonucleotides delivery to cells in culture.

A series of 2,3-dialkyloxypropyl quaternary ammonium lipids containing hydroxyalkyl chains on the quaternary amine were synthesized, formulated with dioleoylphosphatidylethanolamine (DOPE) and assayed for their ability to enhance the activity of an intercellular adhesion molecule 1 (ICAM-1) antisense oligonucleotide, ISIS 1570. Cationic liposomes prepared with hydroxyethyl, hydroxypropyl and hydroxybutyl substituted cationic lipid all enhanced the activity of the ICAM-1 antisense oligonucleotide. Cationic lipids containing hydroxypentyl quaternary amines only marginally enhanced the activity of ISIS 1570. Hydroxyethyl cationic lipids synthesized with dimyristyl (Cl4:0) and dioleyl (C18:1) alkyl chains were equally effective. Activity of cationic lipids containing saturated alkyl groups decreased as the chain length increased, i.e. the dimyristyl (C14:0) was more effective than dipalmityl (C16:0) lipid, which was more effective than distearyl (C18:0). The phase transition temperature of cationic lipids containing saturated aliphatic chains was 56 degrees C for the distearyl lipid, 42 degrees C for the dipalmityl lipid and 24 degrees C for the dimyristyl lipid. Cationic lipids with dioleyl alkyl chains required DOPE for activity, with optimal activity occurring at 50 mole%. In contrast, a dimyristyl containing cationic lipid did not require DOPE to enhance the activity of ISIS 1570. Formulation with different phosphatidylethanolamine derivatives, revealed that optimal activity was obtained with DOPE. These studies demonstrate that several cationic lipid species enhance the activity of phosphorothioate antisense oligonucleotides and provide further information on the mechanism by which cationic lipids enhance the activity of phosphorothioate oligodeoxynucleotides.

Base Sequence↗
PubMed1990

Differential modulation by cations of sigma and phencyclidine binding sites in rat brain.

The present investigation attempted to differentiate haloperidol-sensitive sigma sites (sigma H) from phencyclidine (PCP) binding sites in rat brain membranes. We studied the effects of several cations at physiologically relevant concentrations on the binding of radioligands selective for sigma H sites ([3H]haloperidol, [3H](+)3-PPP**), and [3H](+)SKF10,047), or for PCP sites ([3H]PCP and [3H]TCP). The PCP sites displayed a markedly greater sensitivity to cations than sigma H sites. This property was reflected by a greater extent of inhibition of the binding of PCP-selective relative to sigma H-selective ligands at a given cation concentration, as well as by lower IC50's and by steeper slopes of the cation dose-response curves. Divalent cations were approximately 100 times more potent than monovalent cations. All cations were inhibitory, except Sr2+ and Ba2+ which, at micromolar concentrations, enhanced PCP binding but not sigma H binding. Thus, PCP-selective sites appeared to be distinct from sigma H sites with regards to several aspects of cation modulation. This is consistent with the view that PCP and sigma H sites are distinct molecular entities. Further, the marked cation sensitivity of the PCP site is consistent with the current hypothesis according to which the PCP site is linked to the N-methyl-D-aspartate (NMDA) receptor-cation channel complex.

Animals↗
PubMed2005

Cationic polypeptides are required for anti-HIV-1 activity of human vaginal fluid.

Mucosal surfaces of the vagina are the portals for heterosexual transmission of HIV-1 and therefore play a fundamental role in the pathogenesis of primary infection. In the search for direct biological evidence for the role of human vaginal fluid in innate host defense, we characterized the anti-HIV-1 function of cationic polypeptides within minimally manipulated vaginal fluid. In the current study we revealed that vaginal fluid confers intrinsic anti-HIV-1 properties against both X4 and R5 strains of HIV-1 and could protect against HIV-1 infection and reduce proviral genome integration in organotypic cultures of human cervicovaginal tissue. The majority of this activity was contained in the cationic polypeptide fraction, and the depletion of cationic polypeptides using a selective cation exchange resin ablated most of the intrinsic activity against HIV-1. By adding the cationic polypeptide fraction to depleted vaginal fluid, we were able to restore activity against HIV-1. Using a proteomic approach, we identified 18 cationic polypeptides within vaginal fluid, nearly all of which are either known antimicrobials or have other purported roles in host defense. Interestingly, physiologic concentrations of 13 of the cationic polypeptides were not active alone against HIV-1, yet in concert they partially restored the anti-HIV-1 activity of cation-depleted vaginal fluid. These results suggest that synergism between cationic polypeptides is complex, and full anti-HIV-1 activity probably involves the aggregate of the cationic peptides and proteins in vaginal fluid.

Animals↗
PubMedDate not supplied

Quantitative methods for evaluating optical and frictional properties of cationic polymers.

This paper presents three quantitative methods to examine gloss, opacity, and friction of cationic polymers. The adsorption of cationic polymers onto hair and skin can be regarded as a thin film coating. Therefore, optical and frictional properties of polymer films are of significant relevance to the applications of cationic polymers in hair care products. Such properties reflect the desirable hair condition attributes consumers seek in shampoo and conditioner products. Using these test methods, polyquaternium-10 and cationic guar samples of varying molecular weight and cationic substitution were compared. The effect of an anionic surfactant, sodium dodecyl sulfate (SDS), on polymer film properties was also investigated. Neat guar hydroxypropyl trimonium chloride imparts less friction than polyquaternium-10 but dulls the substrate employed in this study. The optical data show that polyquaternium-10 provides greater film clarity and gloss than cationic guars. In the presence of SDS, polyquaternium-10 also displays similar or lower friction than cationic guar. The comparative optical and frictional results are in good agreement with the visual assessment of the cationic polymer films. These results clearly demonstrate that polyquaternium-10 exhibits superior film properties in the forms of both neat polymer and polymer/surfactant complex. In addition, microscopic techniques such as scanning electron microscopy (SEM) and atomic force microscopy (AFM) provide powerful explanations for the differences noted between the two popular classes of cationic polymers. The test methods described in this paper can be utilized to differentiate the upper performance potential of cationic polymers. These objective and standardized test methods derived from the coatings industry are not affected by the variability of hair or the formulation complexity of end products. They can be useful tools in the product development process in quickly screening the relative performance of different polymers.

Cations↗
PubMed1985

Interaction of valinomycin and monovalent cations with the (Ca2+,Mg2+)-ATPase of skeletal muscle sarcoplasmic reticulum.

The interactions of monovalent cations and of the K+-specific ionophore, valinomycin, with the Ca2+-ATPase of skeletal muscle of sarcoplasmic reticulum have been studied in the absence of cation gradients by their effects on enzyme turnover and on the ATP plus Ca2+-dependent enhanced fluorescence of the ATP analogue, 2',3'-O-(2,4,6-trinitrocyclohexyldienylidine)-adenosine 5'-triphosphate (TNP-ATP) (Watanabe, T., and Inesi, G. (1982) J. Biol. Chem. 257, 11510-11516). Monovalent cations decreased turnover-dependent TNP-ATP fluorescence in the series K+ greater than Rb+ approximately equal to Cs+ greater than Na+ greater than Li+ (K0.5 = 49, 73, 75, 94, and 246 mM, respectively), consistent with the known specificity of the monovalent cation binding site that stimulates turnover and E-P hydrolysis. Valinomycin (200 nmol/mg), in the absence of monovalent cations, decreased ATPase activity by 30% and abolished the stimulatory effects of 150 mM KCl or NaCl on turnover. The ionophore alone enhanced TNP-ATP fluorescence by 20% and altered the specificity and affinity of the site that inhibited TNP-ATP fluorescence to Cs+ greater than Rb+ greater than K+ approximately equal to Na+ greater than Li+ (K0.5 = 79, 111, 134, 136, and 270 mM, respectively), which follows the Hofmeister series for effectiveness of monovalent lyotropic cations. TNP-ATP binding was not affected by either monovalent cations or valinomycin. Inhibition of turnover-dependent TNP-ATP fluorescence appears to be a useful parameter for monitoring monovalent cation binding to the Ca2+-ATPase. It is concluded that the ionophore interacts directly with the Ca2+-ATPase, independent of its K+ conductance effects on the lipid bilayer, and modifies the affinity and specificity of the monovalent cation site, either by direct interaction or by the formation of a valinomycin-monovalent cation-enzyme complex.

Adenosine Triphosphate↗
PubMed1984

Activation of calmodulin by various metal cations as a function of ionic radius.

The active form of calmodulin is a Ca2+ . calmodulin complex. The purpose of this investigation was to determine whether other metal cations substitute for Ca2+ to activate calmodulin. Binding of Ca2+ resulted in an altered conformation of calmodulin with an increased quantum yield in its tyrosine fluorescence. Qualitatively similar results were obtained with Zn2+, Mn2+, Cd2+, Hg2+, Sr2+, Pb2+, Tb3+, Sm3+, and La3+. The relative extents of fluorescence enhancement by these cations were related to their ionic radii: all cations with ionic radii close to Ca2+ (0.99 A) increased tyrosine fluorescence, whereas those with different ionic radii were not effective, or much less so. The change in calmodulin conformation by the cations was confirmed by its altered electrophoretic mobility on polyacrylamide gels. Cations that change the conformation of calmodulin allow it to stimulate phosphodiesterase. The relative extents of stimulation of phosphodiesterase by cations were also related to their ionic radii. Finally, the ability of metal cations to inhibit Ca2+ binding was similarly related to their ionic radii. In general, the closer the radius of a metal cation was to that of Ca2+, the more effective was the cation to substitute for Ca2+. The range of effective ionic radii was approximately 1 +/- 0.2 A. Calmodulin-stimulated phosphodiesterase activity by the cations was reversed by trifluoperazine, an antagonist of calmodulin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Nonselective cation channel activated by patch excision from lobster olfactory receptor neurons.

A nonselective cation channel activated by patch excision was characterized in inside-out patches from spiny lobster olfactory receptor neurons. The channel, which was permeable to Na+, K+ and Cs+, had a conductance of 320 pS and was weakly voltage dependent in the presence of micromolar divalent cations. Millimolar internal divalent cations caused a voltage- and concentration-dependent block of Na+ permeation. Analysis of the voltage dependence indicated that the proportion of the membrane's electric field sensed by Mg2+ was greater than 1, suggesting that the channel contains a multi-ion pore. Internal divalent cations also reduced the frequency of channel opening in a concentration-dependent, but not voltage-dependent, manner, indicating that different cation binding sites affect gating and conductance. While block of gating prevented determining if internal divalent cations permeate the channel, a channel highly permeable to external divalent cations was observed upon patch excision to the inside-out configuration. The monovalent and divalent cation conductances shared activation by patch excision, weak voltage dependence, and steady-state activity, suggesting that they are the same channel. These data extend our understanding of this type of channel by demonstrating permeation by monovalent cations, detailing Mg2+ block of Na+ permeation, and demonstrating the channel's presence in arthropods.

Animals↗
PubMed1998

A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats.

We have identified a unique structural transition (in slow exchange on the NMR time scale) in the tertiary fold of the d(G-G-G-C-T4-G-G-G-C) quadruplex on proceeding from Na+ to K+ as counterion in aqueous solution. Both monovalent cation-dependent conformations exhibit certain common structural features, which include head-to-tail dimerization of two symmetry-related stem-hairpin loops, adjacent strands which are antiparallel to each other and adjacent stacked G(syn).G(anti). G(syn).G(anti) tetrads in the central core of the quadruplexes. The Na and K cation stabilized structures of the d(G-G-G-C-T4-G-G-G-C) quadruplexes differ in the conformations of the T-T-T-T loops, the relative alignment of G.C base-pairs positioned opposite each other through their major groove edges and potentially in the number of monovalent cation binding sites. We have identified potential K cation binding cavities within the symmetry-related T-T-T-G segments, suggesting the potential for two additional monovalent cation binding sites in the K cation-stabilized quadruplex relative to its Na cation-stabilized counterpart. Modeling studies suggest that the major groove edges of guanine residues in Watson-Crick G.C base-pairs could potentially be bridged by coordinated K cations in the d(G-G-G-C-T4-G-G-G-C) quadruplex in KCl solution in contrast to formation of G.C.G.C tetrads for the corresponding quadruplex in NaCl solution. Our results defining the molecular basis of a Na to K cation-dependent conformational switch in the loop spanning segment of the d(G-G-G-C-T4-G-G-G-C) quadruplex may have relevance to recent observations that specific K cation coordinated loop conformations within quadruplexes exhibit inhibitory activity against HIV integrase.

Binding Sites↗