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PubMed1979

Photosensory transduction in the flagellated alga, Euglena gracilis I. Action of divalent cations, Ca2+ antagonists and Ca2+ ionophore on motility and photobehavior.

1. The flagellated alga, Euglena gracilis, swims forward essentially in a straight path under constant light intensity. Strong motility of the cells can be supported by Mg2+ alone but optimum motility is found in the presence of Mg2+, Ca2+ and K+. 2. Ca2+, Co2+, Mn2+ and Ba2+ induce a concentration-dependent increase in the rate at which the cells change the direction of their swimming path (a klinokinesis). Ni2+ immobilizes the flagellum. 3. On perception of a reduction ('step-down stimulus') in blue light intensity in their environment, Euglena rotate in place (tumble) for a finite period (the step-down photophobic response). 4. The duration of the tumbling is enhanced in the presence of divalent cations following the series Ca2+ greater than Ba2+ greater than Mn2+ greater than Co2+ greater than Mg2+ = Ni2+ = 0. 5. Neither the tumbling response in the presence of low concentrations of Ca2+ or the Ca2+-stimulated response is altered by verapamil (a Ca2+ conductance antagonist). The Ca2+ conductance/active transport antagonist, ruthenium red, is also inactive. 6. The Ca2+ ionophore, A23187, has little effect on flagellar activity in the absence of extracellular Ca2+. However, in the presence of A23187, Ca2+ induces a specific light-independent, concentration-dependent discontinuous tumbling response of the cells. 7. The data support a role for Ca2+ and Mg2+ in control of flagellar activity. However, blue light-induced tumbling behavior would not appear to be the direct result of a light-mediated alteration in the Ca2+ conductance of the flagellar membrane to affect flagellar reorientation. The results are discussed in connection with previous theories on control of flagella activity in green alga.

Anti-Bacterial Agents↗
PubMed1988

A hydrophobic region on myosin light chains modulated by divalent cations.

A hydrophobic region was detected on several types of myosin light chain by enhancement of the quantum yield of 1-anilino-8-naphthalenesulfonate (ANS) fluorescence. The character of this non-polar region was altered by the binding of Ca2+ or Mg2+ to the light chain, the quantum yield of the ANS being increased, and its emission maximum undergoing a blue-shift. These changes enabled the binding of divalent cations to the myosin light chains to be monitored. When Ca2+ was bound to gizzard regulatory light chain, a biphasic enhancement of light-chain-bound ANS fluorescence occurred, the first phase taking place in the micromolar range and the second in the millimolar range of free Ca2+ concentration. Enhancement of protein-bound ANS fluorescence as divalent cations were bound was also observed with other types of myosin light chain.

Anilino Naphthalenesulfonates↗
PubMed1983

Effects of prostaglandins and divalent cations on cAMP production in isolated rat hepatocytes.

In intact hepatocytes, prostaglandin E2 (PGE2) inhibits up to 60% of the cyclic AMP (cAMP) formation in response to glucagon. PGE2 was found also to inhibit cAMP production in response to Mn2+, and Mn2+ counteracted the effect of PGE2 on the response to glucagon. However, when added to cells with ruptured plasma membranes, PGE2 had no effect on cAMP production, even though the ruptured cells had an equally strong response to glucagon as did intact cells. Only when cells were ruptured in the presence of PGE2 and incubated as very dense suspensions did PGE2 inhibit a response to glucagon up to 20%. These results may be explained by assuming the existence of a cytosolic factor necessary for transmitting the inhibitory effect of PGE2. The role of divalent cations in cAMP formation in intact cells was investigated. After extraction of cations with ethylenediamine-tetraacetic acid (EDTA), cAMP production in response to glucagon was reduced by more than 60%. Addition of Mn2+ restored cAMP formation completely, whereas Mg2+ was somewhat less effective, and Ca2+ could not restore any activity. Even low concentrations of Ca2+ appeared under certain conditions to repress adenylate cyclase activity.

Animals↗
PubMed1997

Modulation of GABAC response by Ca2+ and other divalent cations in horizontal cells of the catfish retina.

GABAC responses were recorded in cultured cone-driven horizontal cells from the catfish retina using the patch clamp technique. At a holding potential of -49 mV, a bicuculline-resistant inward current (IGABA) was observed when 10 microM GABA was applied. The amplitude of IGABA increased as the extracellular Ca2+ ([Ca2+]o) was increased. Concentration-response curves of IGABA at 2.5 and 10 mM -Ca2+-o had similar EC50 (3.0 and 3.1 microM) and Hill coefficients (1.54 and 1. 24). However, the maximal response estimated at 10 mM [Ca2+]o was larger than the maximal response at 2.5 mM [Ca2+]o. Increasing Ca influx through voltage-gated Ca channels and the resulting rise in the intracellular Ca2+ concentration had no effects on IGABA. However, IGABA was inhibited by extracellular divalent cations, with the following order of the inhibitory potency: Zn2+ > Ni2+ > Cd2+ > Co2+. The inhibitory action of Zn2+ on the [Ca2+]o-dependent IGABA increase was noncompetitive. The action of [Ca2+]o on IGABA was mimicked by Ba2+ or Sr2+. These results demonstrate that the extracellular domain of GABAC receptors has two functionally distinct binding sites represented by Ca2+ (facilitation) and Zn2+ (inhibition). Since [Ca2+]o and [Zn2+]o change into the opposite direction by light, it seems likely that they modify cooperatively the efficacy of the positive feedback consisting of the GABAC receptor.

Animals↗
PubMed1985

High and low affinity states of the dihydropyridine and phenylalkylamine receptors on the cardiac calcium channel and their interconversion by divalent cations.

Drug receptors associated with Ca2+-channels in isolated chick heart membranes were found to exist in high and low affinity states. When assays were conducted in the presence of EDTA most of the receptors detected with the dihydropyridines (+)[3H]PN 200-110 or [3H]nitrendipine appeared to be in the lower affinity state. Inclusion of either Mg2+ or Ca2+ in the binding reactions resulted in the disappearance of the lower affinity state and the conversion of the receptors to a single high affinity state. Similar results were obtained with the phenylalkylamine derivative [3H]desmethoxyverapamil (D888). The results suggest that both the dihydropyridine and phenylalkylamine receptors on the cardiac Ca2+-channel can exist in interconvertible high and low affinity states in vitro, and that the proportion of receptors in each affinity state can be altered by the absence or presence of divalent cations.

Animals↗
PubMed1977

H+ translocation in lysozyme-treated cells of the blue-green alga Plectonema boryanum. Difference between isotonically and hypotonically treated preparations and effects of divalent cations.

Lysozyme-treated cells of a blue-green alga, Plectonema boryanum, had an internal pH of 7.3+/-0.2 under isotonic and hypotonic conditions. This value was similar to that of untreated cells. The CCCP-induced biphasic H+ change seen in the isotonic cells was not observed in the hypotonically treated cells. The biphasic time course remained in the hypotonic preparation if CaCl2 or MgCl2 was added prior to the osmotic shock. It is suggested that the cells have two compartments of H+ concentration. The outer region may be more acidic than the inner region. A light-induced H+ efflux was observed under isotonic conditions and an influx of H+ under hypotonic conditions. The H+ influx was not observed when lysozyme-treated cells were incubated with CaCl2 or MgCl2 prior to the hypotonic treatment. Two types of effects of divalent cations, one on the rigidity of the outer membrane and another on the permeability characteristics of the inner photosynthetic membrane, are indicated. Rearrangement of the photosynthetic membranes and an apparent inversion of the H+ pump by hypotonic shock are also suggested.

Biological Transport, Active↗
PubMed2002

Structure and properties of hydrophobically end-capped poly(ethylene oxide) solutions in the presence of monovalent and divalent cations.

Hydrophobically modified poly(ethylene oxide), HMPEO, was studied in concentrated salt solutions. The influence of salts was compared to the effect of temperature on poly(ethylene oxide), PEO. As expected, the addition of monovalent cations (Na(+), K(+)) has the same effect as an increase in temperature in agreement with the thermodynamic properties of PEO: a decrease in solubility, micelle size, and viscosity was observed. Moreover, the intensity of neutron scattering peaks (characteristic of the semi-dilute solutions of these associative polymers) increases due to the collapse of PEO coronae in micelles. Very peculiar behavior was observed in the presence of divalent cations (Ca(2+), Mg(2+)): larger micelle aggregates and higher viscosities, relaxation times, and activation energies were observed by dynamic rheology. This behavior is attributed to interactions between divalent cations and oxygen in PEO backbones close to the micelle core, which may reinforce intermicellar bridges.

Journal Article↗
PubMed1994

Interactions of liposome bilayers composed of 1,2-diacyl-3-succinylglycerol with protons and divalent cations.

Bilayer liposomes were prepared by using pure DOSG (1,2-dioleoyl-3-succinylglycerol) or DPSG (1,2-dipalmitoyl-3-succinylglycerol) at pH 7.4 or above. These liposomes undergo destabilization upon incubation with acid. When calcein was used as an entrapped aqueous marker, half maximal content leakage was observed between pH 5.8-6.3. Differential scanning calorimetry showed that at pH 7.4, the chain-melting temperature (Tm) of DPSG was 60.4 degrees C, and increased with decreasing pH (Tm = 57.0 degrees C and 62.7 degrees C at pH 8.9 and 6.7, respectively). Below pH 6.7, extensive phase separation occurred as the major chain melting peak split into three peaks. These three peaks coalesced into one peak below pH 5. Freeze fracture electron micrographs of DOSG liposomes at pH 4 showed the formation of non-bilayer as well as hexagonal phase structures. The effects of divalent cations, such as Ca2+ and Mg2+, on the destabilization of DASG bilayers have also been studied. Differential scanning calorimetry studies of bilayers composed of DPSG showed that both Ca2+ and Mg2+ could increase the Tm of DPSG with increasing concentrations. However, under identical conditions Mg2+ was more effective than Ca2+ in increasing the Tm of DPSG. X-ray diffraction indicated that both Ca2+ and Mg2+ could induce DPSG bilayers to undergo a complete lamellar to hexagonal phase transition. There was a size-dependency on the plasma stability of DOSG liposomes. DOSG liposomes that were smaller in size were more stable in plasma than the larger ones. After incubation with plasma, DOSG liposomes became less acid-sensitive. DOSG immunoliposomes entrapping diphtheria toxin A chain were used as a model for cytoplasmic delivery of the novel pH-sensitive liposomes. The delivery activity was comparable to that of the conventional pH-sensitive liposomes containing unsaturated phosphatidylethanolamine. Our data indicate that the mechanism of liposome destabilization involves extensive bilayer phase separation as well as the formation of non-bilayer structures.

Calorimetry, Differential Scanning↗
PubMed1978

Selective release of excreted DNA sequences from phytohemagglutinin-stimulated human peripheral blood lymphocytes. Effects of trypsin and divalent cations.

We studied the synthesis of excreted DNA sequences and their release from phytohemagglutinin-stimulated human peripheral blood lymphocytes under conditions permitting optimal cell growth. Cells were labeled by constant exposure to low specific activity [3H]thymidine. Excreted DNA sequences were synthesized during the period of logarithmic cell growth and moved slowly from the high molecular weight chromosomal DNA fraction into the low molecular weight cell DNA fraction (Hirt supernate) from which they could be specifically released by treating the cells briefly with small amounts of various proteases; 1 microgram/ml trypsin for 5 min was optimal. On day 5 of culture, 13.3 +/- 6.9% of the total cellular acid-precipitable [3H]thymidine was released by this treatment. Trypsin-induced release was partially and reversibly inhibited by incubating the cells for 16 h with 5 mM dibutyryl-cyclic AMP. Cells incubated in the absence of divalent cations spontaneously released this Hirt supernatant DNA; after maximal release had occurred under these circumstances, additional trypsin treatment caused no further release of DNA. Trypsin-induced DNA release could be completely and reversibly inhibited by incubating the cells in the presence of 10 mM calcium. Trypsin-released DNA was isolated and analyzed by reassociation kinetics. A major component, representing 54% of the DNA, reassociated with a C0t1/2 of 68 mol.s/liter (the value at which DNA association is 50% complete). The reassociation of this DNA was studied in the presence of an excess of DNA isolated from stimulated lymphocytes on day 3 in culture, and in the presence of an excess of resting lymphocyte DNA. The high molecular weight fraction of day-3 cell DNA contained three times more copies of the trypsin-released DNA major component as compared to resting lymphocyte DNA. Hirt supernatant DNA isolated from day-5 stimulated lymphocytes reassociated in an intermediate component representing 34% of the DNA with a Cot1/2 of mol.s/liter; after cells were treated with trypsin, this component could no longer be identified in the Hirt supernatant fraction, presumably because it had been released into the incubation medium. These data describe a quantitatively reproducible system with which synthesis and release of excreted DNA sequences can be studied.

Bucladesine↗
PubMedDate not supplied

Binding of divalent cations by canine cardiac myosin: differences in normal right and left ventricles dependent upon number of light chains.

The moles of calcium bound by the left ventricle were 1.5 +/- 0.1, while those of the right ventricle were 2.9 +/- 0.2. The calcium binding constants were the same between myosins of the two cardiac ventricles. The Ca2+ binding constants were approximately 1.1 X 10(5) M-1 for both left and right ventricular myosins. Left ventricular myosin bound 1.3 +/- 0.1 mol of Mn2+, whereas right ventricular myosin bound 2.8 +/- 0.1 mol of Mn2+. The divalent cation Mn2+ only partially competed out Ca2+ (50%). Because of the partial competition, it seemed that Ca2+ and Mn2+ had some sights in common. These studies demonstrate a twofold difference in divalent cation binding (Ca2+, Mn2+) between left and right ventricular myosins. This variation in cation binding between the two ventricles is reflected in similar differences in myosin ATPase activity between the two ventricles.

Adenosine Triphosphatases↗
PubMed1993

Fast and slow blockades of the inward-rectifier K+ channel by external divalent cations in guinea-pig cardiac myocytes.

The present patch-clamp study shows that external Mg2+, Ca2+ and Sr2+ decrease the unit amplitude of inward current through the inward-rectifier K+ channel in a concentration-dependent manner. Sr2+ produces a voltage-dependent flickering block as well, and the fractional electrical distance between the external orifice and the Sr2+ binding site (delta) is 0.73. The decrease of unit amplitude is reversible and voltage independent while it does not increase the noise level on the open-channel current. Unit current decreased by Mg2+ or Ca2+ has a longer mean open time, which is inversely proportional to the unit amplitude. External Mg2+ does not decrease the amplitude of unit outward current. A surface potential shift, measured using voltage-dependent Cs+ block (delta = 1.60), failed to explain the current decrease. Therefore, we conclude that (1) the external divalent cations cause an extremely fast channel block, which appears as a decreased amplitude of the unit current on the recording system; (2) the blocking site (fast site) is present near the external orifice of the channel, and it is separate from the blocking site (slow site) to which Cs+ and Sr2+ bind.

Animals↗
PubMed1994

Characterization of cell surface material removed by water and NaCl washing of Paracoccus denitrificans grown under conditions of divalent cation deficiency and sufficiency.

Paracoccus denitrificans grown on complex medium deficient in Mg2+ and Ca2+ are rendered lysozyme susceptible by washing with NaCl, whereas cells grown in a succinate-salts medium (Mg2+ and Ca2+ sufficient) or complex medium supplemented with Mg(2+)+Ca2+ are not. The material released by water washing of cells grown on complex medium and complex medium supplemented with Mg2+ and Ca2+ was characterized by a high protein content. There was a high lipid: protein ratio and an appreciable amount of 3-deoxyoctulosonic acid in the material released by NaCl washing of cells grown under all conditions, indicating release of outer membrane material. The lipid ornithine: lipid phosphorous ratios of NaCl wash from cells grown on complex medium and complex medium supplemented with Mg2+ and Ca2+ were 0.54 and 0.34, respectively. Although NaCl washing removed outer membrane material from cells grown under all conditions, only divalent cation deficient cells were rendered lysozyme susceptible. This might be explained by the increased outer membrane ornithine-containing lipid to phospholipid ratio in these cells yielding a more permeable outer membrane.

Cations, Divalent↗
PubMed1990

Effects of resection on absorption and secretion of divalent cations by small intestine of rat.

Resection increases villus height and crypt depth of remaining intestine. We examined functional consequences of resection by measuring absorption of strontium and secretion of calcium and magnesium by proximal and distal segments remaining after resecting 70% of mid small intestine. Compared with the transected control group, resection decreased strontium absorption per unit weight of mucosa (specific absorption) in the proximal segment. The decreased specific absorption was compensated by increased mucosal growth in the resected group so that absorption per unit length of segment (per cm) was the same in both groups. Resection increased secretion of calcium and magnesium by 66% per unit weight of mucosa and by 145%/cm in the distal segment. Comparing proximal with distal segments in the resected group, secretion was greater in distal for calcium and in proximal for magnesium. Intestinal resection causes responses in absorption and secretion of divalent cations important in mineral homeostasis.

Animals↗
PubMed1992

Modulation of the mitochondrial permeability transition pore. Effect of protons and divalent cations.

We have studied the induction of the mitochondrial cyclosporin A-sensitive permeability transition pore (PTP) by the bifunctional SH group reagent phenylarsine oxide (PhAsO). Addition of nanomolar concentrations of the electroneutral H(+)-K+ ionophore nigericin to nonrespiring mitochondria in sucrose medium determines a dramatic increase of the time required for PTP induction by PhAsO, while no effect of nigericin is apparent in KCl medium. Using mitochondria loaded with the internal pH indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, we show that the effect of nigericin is mediated by the ionophore-induced acidification of matrix pH. Indeed, experimental manipulation of pHi by a number of treatments indicates that PTP induction is directly related to matrix pH, in that the PTP induction process becomes slower as pHi decreases at constant pHo. PTP induction by PhAsO in respiration-inhibited mitochondria is stimulated by Ca2+ and inhibited by a series of divalent cations. Since PhAsO induces the PTP even in the presence of excess EGTA and in the absence of respiration (Lenartowicz, E., Bernardi, P., and Azzone, G.F. (1991) J. Bioenerg. Biomembr. 23, 679-688), we have been able to study the Ca2+ dependence of the induction process. We show that the apparent Km for Ca2+ activation is about 10(-5) M and that Ca2+, cyclosporin A, and inhibitory Me2+ ions behave as if they were competing for the same binding site(s) on the pore. Since similar results are obtained from patch-clamp experiments on the mitochondrial megachannel (Szabó, I., Bernardi, P., and Zoratti, M. (1992) J. Biol. Chem. 267, 2940-2946), we suggest that (i) the PTP and the mitochondrial megachannel are the same molecular structures and (ii) the same factors affect both the process of pore induction and its open-closed orientation.

Arsenicals↗
PubMed2002

The activation of neuronal nitric-oxide synthase by various divalent cations.

Nitric-oxide synthase (NOS; EC 1.14.13.39) catalyzes the oxidation of L-arginine to nitric oxide (NO(.)) and L-citrulline via the intermediate N(omega)-hydroxy-L-arginine. Of the three distinct isoforms of NOS that have been characterized, the constitutive neuronal NOS (NOS I) generates NO(.) associated with long-term potentiation (LTP) and early brain development. All of the NOS isoforms contain an N-terminal oxidase and a C-terminal reductase domain connected by a Ca(2+)/calmodulin binding region. To activate NOS I, Ca(2+) has to bind to calmodulin, allowing electron transport through both domains. Calcium ions are tightly regulated in cells. However, a number of other metal ions that bind and activate calmodulin may also activate NOS I. One such metal ion may be Pb(2+), which is associated with neurobehavioral and psychological alterations, including the inhibition of LTP. The effect of various divalent cations on NOS I activity was tested, and the results presented herein demonstrate that Pb(2+) and Sr(2+) can activate NOS I to a level similar to that found for Ca(2+). Finally, there is a synergy between Pb(2+) and Ca(2+) resulting in maximal activation of NOS I using minimal concentrations of both metal ions.

Animals↗
PubMed1980

Divalent cations and vitamin B12 uptake by intestinal brush-border membrane vesicles.

Brush-border membrane vesicles from hamster intestine were employed to investigate uptake (binding) of vitamin B12 (B12). Ileal vesicles took up 25 times more B12 than did jejunal vesicles. Uptake of B12 by ileal vesicles was dependent on intrinsic factor (IF) and required Ca2+. Increasing the Ca2+ concentration caused an increase in uptake of B12 reaching a maximum at approximately 8 mM Ca2+. At high Ca2+ concentrations, 6-8 mM, Mg2+ had little effect on uptake of B12. At low Ca2+ concentrations, up to 2 mM, Mg2+ stimulated B12 uptake. Mg2+, Mn2+, and, to a lesser extent, Sr2+ stimulated Ca2+-dependent B12 uptake, but Zn2+, Ba2+, Na+, K+, and La3+ did not. B12 was apparently not metabolized and was bound as IF-B12 complex, which could be removed with (ethylenedinitrilo)tetraacetic acid (EDTA). Our results suggest that two types of divalent cation reactive sites are involved in binding of IF-B12. One is Ca2+ specific. The other is less specific reacting with Mg2+, Mn2+, Sr2+, and perhaps Ca2+ itself, thereby stimulating Ca2+-dependent binding of IF-B12 to its ileal receptor.

Animals↗
PubMed1975

Maintenance of feedback regulation of filtration dynamics in the absence of divalent cations in the lumen of the distal tubule.

In the present experiments we have studied the hypothesis that the feedback responses of glomerular capillary pressure and glomerular filtration rate to elevated distal fluid delivery depend to some extent on the luminal concentration of calcium or magnesium [1]. Loops of Henle were therefore perfused with the following solutions which were designed to yield wide variations of distal divalent cation concentration: 1. Ringer, 2. 140mM NaCl, 3. 125mM NaCl + 10mM CaCl2, 4. 125 mM NaCl + 10 mM MgCl2, 5. 125 mM NaCl + 10 mM Na citrate, and 6. 125 mM NaCl + 10 mM EDTA. During orthograde perfusion with these solutions stop flow pressure (SEP) and early proximal flow rate (EPFR) were measured in each nephron at perfusion rates of 0, 15, 30, and 45 nl/min. We found that perfusion with solutions 2 to 6 did not significantly modify the flow induced change of SFP or EPFR observed during Ringer perfusion. To expose the macula densa cells to chemically well defined solutions loops of Henle were retrogradely perfused from the distal tubule and EPFR was measured in a given nephron with and without perfusion. Identical reductions of EPFR were induced by retrograde perfusions with 140 mM NaCl, 125 mM NaCl + 10 mM CaCl2, and 125 mM NaCl + 10 mM EDTA. Furthermore, an almost complete blunting of the feedback response was noted during retrograde perfusion with 25 mM NaCl. Addition of 5 mM CaCl2 failed to restore the feedback reaction. These results do not support the concept that luminal divalent cations participate in the initiation of tubulo-glomerular feedback responses.

Animals↗
PubMed1994

Subunit-selective mutagenesis of Glu-89 residue in human immunodeficiency virus reverse transcriptase. Contribution of p66 and p51 subunits to nucleoside analog sensitivity, divalent cation preference, and steady state kinetic properties.

The E89G alteration in the human immunodeficiency virus type 1 reverse transcriptase has been shown to confer resistance to nucleoside analogs and a loss of magnesium cation preference (Prasad, V.R., Lowy, I., De Los Santos, T., Chiang, L., and Goff, S.P. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 11363-11367. The wild type reverse transcriptase heterodimer, chimeric reverse transcriptases that contain the E89G alteration in one of the subunits (p66wt/p51m and p66m/p51wt), and the mutant enzyme (p66m/p51m) were prepared. Analysis of steady state kinetic parameters showed that the mutant enzyme (p66m/p51m) displayed a higher Vmax, a higher Km for 2'-deoxythymidine triphosphate, and a higher Ki for 2',3'-dideoxythymidine triphosphate than the wild type enzyme. The increased Km and Ki values were observed only when a heterodimer contained the alteration in the p66 subunit. Tests for divalent cation requirement showed that only the dimers containing the wild type p66 (p66wt/p51wt and p66wt/p51m) displayed a preference for magnesium. Our results indicate that p66 plays a dominant role in deoxynucleotide triphosphate substrate recognition (Km), nucleoside analog sensitivity (Ki), and magnesium preference. However, the increased Vmax displayed by the mutant enzyme (p66m/p51m) appeared to be determined by both of the subunits.

Base Sequence↗