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1.
Abstract: The present study reports the ion dependency of 2β-carbomethoxy-3β-(4-fluorophenyl)[3 H]tropane ([3 H]- CFT) binding to the dopamine transporter in the rat striaturn. The results indicate that [3 H]CFT binding to synaptosomal P2 membranes requires low concentrations of Na+ (peak binding between 20 and 50 m M Na+ ), is stimulated by phosphate anion or l- , but is unaffected or only slightly affected by F- , Cl- , Br- , NO3 - , or SO4 2- , Concentrations of Na+ of >50 m M become inhibitory except in the presence of l- , which shifts peak binding levels toward higher Na+ concentrations and also elevates the peak binding level. K+ strongly decreased [3 H]CFT binding with a shallow inhibition curve, and Na+ could not overcome this effect. Saturation analysis of [3 H]CFT binding revealed a single binding site changing its affinity for CFT depending on the concentration of sodium phosphate buffer (6, 10, 30, 50, 130, or 200 m M ; 1 mM plus 49 mM NaCIversus 10 m M plus 40 m M NaCI; or 1 mM plus 129 m M Nal versus 10 m M plus 120 m M Nal). No differences were observed in the density of CFT binding sites between any of the conditions examined. 相似文献
2.
3.
《Bioorganic & medicinal chemistry》2016,24(18):4410-4414
We have cloned, purified and investigated the catalytic activity and anion inhibition profiles of a full catalytic domain (358 amino acid residues) carbonic anhydrase (CA, EC 4.2.1.1) from Plasmodium falciparum, PfCAdom, an enzyme belonging to the η-CA class and identified in the genome of the malaria-producing protozoa. A truncated such enzyme, PfCA1, containing 235 residues was investigated earlier for its catalytic and inhibition profiles. The two enzymes were efficient catalysts for CO2 hydration: PfCAdom showed a kcat of 3.8 × 105 s−1 and kcat/Km of 7.2 × 107 M−1 × s−1, whereas PfCA showed a lower activity compared to PfCAdom, with a kcat of 1.4 × 105 s−1 and kcat/Km of 5.4 × 106 M−1 × s−1. PfCAdom was generally less inhibited by most anions and small molecules compared to PfCA1. The best PfCAdom inhibitors were sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid, which showed KIs in the range of 9–68 μM, followed by bicarbonate, hydrogensulfide, stannate and N,N-diethyldithiocarbamate, which were submillimolar inhibitors, with KIs in the range of 0.53–0.97 mM. Malaria parasites CA inhibition was proposed as a new strategy to develop antimalarial drugs, with a novel mechanism of action. 相似文献
4.
This paper presents the work conducted on the
chemical constituents of some common and widely distributed
halophyte taxa from Cyprus with the aim that these studies will
help in the evaluation of halophytes for different economical
purposes. The plant species of Crithmum maritimum L., Limbarda
crithmoides (L.) Dumort, Atriplex portulacoides L., Salsola kali L.,
Atriplex halimus L., Limonium oleifolium Mill., L. meyeri (Boiss.)
Kuntze; and Tetraena alba (L.f.) Beier & Thulin were collected
in the middle of July. The shoot tissue and leaf samples were
collected from the natural habitats and left for drying under air
circulation followed by placing them in oven at 60 °C for 96
hours. The material was crushed using mortar and pestle and
subjected to an analysis of macro- and micro-nutrients and
biochemical compounds. K+/Na+ in the leaf tissues of the dicot
species showed relatively high values depicting their behavior
as Na+ includes but very low Cl- levels were recorded. Out of
the species investigated here in 4 TFAA content was rather high.
Values ranging from 0.5% to 1% dry weight were exhibited in one
species. However, only 3 species showed very low TFAA values.
Later may be due to low nitrogen availability in their environment.
The phenetic analyses of eight halophyte species performed on
the data matrix using Ntsys-pc program version 2.1 revealed
that, cluster analysis of the overall results obtained here leads to
2 clusters. This discrimination appears to be as a result of their
different abilities to accumulate either proline or glycine betaine. 相似文献
5.
Four new polyoxometalate compounds built on Preyssler anions and trivalent lanthanide cations, Na2[{Ce(H2O)8}4{Na(H2O)P5W30O110}] · 12H2O (1), H4Na4[Nd2(H2O)14{Na(H2O)P5W30O110}] · 22H2O (2), K2Na[Eu3(H2O)14(HNA)3{Eu(H2O)P5W30O110}] · 3H2O (3 NA = nicotinic acid) and H2[Ce4(H2O)16(HNA)6{Na(H2O)P5W30O110}] · 12H2O (4) have been synthesized and characterized by elemental analysis, IR, TG and single crystal X-ray diffraction. Compound 1 exhibits a tetrasupporting polyoxometalate cluster structure where four {Ce(H2O)8}3+ fragments are supported on the [Na(H2O)P5W30O110]14− cluster. Compound 2 shows a one-dimensional chain structure built from [Na(H2O)P5W30O110]14− clusters linked by Nd3+ cations. Compound 3 displays a one-dimensional chain structure constructed of [Eu(H2O)P5W30O110]12− clusters bridged by Eu3+ cations. Compound 4 has a 2D network formed by 1D chains and {Ce2(H2O)6(HNA)6}6+ linkers. Compounds 2-4 represent the first extended structures based on Preyssler anions. In addition, the fluorescent activity of compound 3 is reported. 相似文献
6.
7.
Binding of the benzodiazepine inverse agonist [3H]methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate [( 3H]DMCM) and the agonist [3H]flunitrazepam [( 3H]FNZ) was compared in rat cortical membranes. Halide ions enhanced [3H]DMCM binding three- to fourfold, increasing both the apparent affinity and the number of binding sites for this radioligand. The effect was present at both 0 and 37 degrees C. In contrast, the magnitude of halide stimulation of [3H]FNZ binding was much smaller, resulting solely from an increase in the apparent affinity for this radioligand, and was not observed at 37 degrees C. The potencies but not the efficacies of a series of anions to stimulate both [3H]DMCM and [3H]FNZ binding to benzodiazepine receptors were highly correlated with their relative permeabilities through gamma-aminobutyric acid (GABA)-gated chloride channels. Two stress paradigms (10 min of immobilization or ambient-temperature swim stress), previously shown to increase significantly the magnitude of halide-stimulated [3H]FNZ binding, did not significantly affect [3H]DMCM binding. Phospholipase A2 treatment of cortical membrane preparations was equipotent in preventing the stimulatory effect of chloride on both [3H]DMCM and [3H]FNZ binding. These data strongly suggest that anions modify the binding of [3H]DMCM and [3H]FNZ by acting at a common anion binding site that is an integral component of the GABA/benzodiazepine receptor chloride channel complex. 相似文献
8.
《Bioorganic & medicinal chemistry》2016,24(16):3413-3417
Among the numerous metalloenzymes known to date, carbonic anhydrase (CA, EC 4.2.1.1) was the first zinc containing one, being discovered decades ago. CA is a hydro-lyase, which catalyzes the following hydration–dehydration reaction: CO2 + H2O ⇋ HCO3− + H+. Several CA classes are presently known, including the α-, β-, γ-, δ-, ζ- and η-CAs. In prokaryotes, the existence of genes encoding CAs from at least three classes (α-, β- and γ-class) suggests that these enzymes play a key role in the physiology of these organisms. In many bacteria CAs are essential for the life cycle of microbes and their inhibition leads to growth impairment or growth defects of the pathogen. CAs thus started to be investigated in detail in bacteria, fungi and protozoa with the aim to identify antiinfectives with a novel mechanism of action. Here, we investigated the catalytic activity, biochemical properties and anion inhibition profiles of the three CAs from the bacterial pathogen Vibrio cholera, VchCA, VchCAβ and VchCAγ. The three enzymes are efficient catalysts for CO2 hydration, with kcat values ranging between (3.4 − 8.23) × 105 s−1 and kcat/KM of (4.1 − 7.0) × 107 M−1 s−1. A set of inorganic anions and small molecules was investigated for inhibition of these enzymes. The most potent VchCAγ inhibitors were N,N-diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, with KI values ranging between 44 and 91 μM. 相似文献
9.
S. Bröer A. Schuster C.A. Wagner A. Bröer I. Forster J. Biber H. Murer A. Werner F. Lang A.E. Busch 《The Journal of membrane biology》1998,164(1):71-77
Expression of the protein NaPi-1 in Xenopus oocytes has previously been shown to induce an outwardly rectifying Cl− conductance (GCl), organic anion transport and Na+-dependent P
i
-uptake. In the present study we investigated the relation between the NaPi-1 induced GCl and P
i
-induced currents and transport. NaPi-1 expression induced P
i
-transport, which was not different at 1–20 ng/oocyte NaPi-1 cRNA injection and was already maximal at 1–2 days after cRNA
injection. In contrast, GCl was augmented at increased amounts of cRNA injection (1–20 ng/oocyte) and over a five day expression period. Subsequently
all experiments were performed on oocytes injected with 20 ng/oocytes cRNA. P
i
-induced currents (Ip) could be observed in NaPi-1 expressing oocytes at high concentrations of P
i
(≥ 1 mm P
i
). The amplitudes of Ip correlated well with GCl. Ip was blocked by the Cl− channel blocker NPPB, partially Na+-dependent and completely abolished in Cl− free solution. In contrast, P
i
-transport in NaPi-1 expressing oocytes was not NPPB sensitive, stronger depending on extracellular Na+ and weakly affected by Cl− substitution. Endogenous P
i
-uptake in water-injected oocytes amounted in all experiments to 30–50% of the Na+-dependent P
i
-transport observed in NaPi-1 expressing oocytes. The properties of the endogenous P
i
-uptake system (K
m
for P
i
> 1 mm; partial Na+- and Cl−-dependence; lack of NPPB block) were similar to the NaPi-1 induced P
i
-uptake, but no Ip could be recorded at P
i
-concentrations ≤3 mm. In summary, the present data suggest that Ip does not reflect charge transfer related to P
i
-uptake, but a P
i
-mediated modulation of GCl.
Received: 22 October 1997/Revised: 24 March 1998 相似文献
10.
H. Ramos E. Valdivieso M. Gamargo F. Dagger B.E. Cohen 《The Journal of membrane biology》1996,152(1):65-75
The polyene antibiotic amphotericin B (AmB) is known to form two types of ionic channels across sterol-containing liposomes,
depending on its concentration and time after mixing (Cohen, 1992). In the present study, it is shown that AmB only kills
unicellular Leishmania promastigotes (LPs) when aqueous pores permeable to small cations and anions are formed. Changes of membrane potential across
ergosterol-containing liposomes and LPs were followed by fluorescence changes of 3,3′ dipropylthiadicarbocyanine (DiSC3(5)). In KCl-loaded liposomes suspended in an iso-osmotic sucrose solution, low AmB concentrations (≤0.1 μm) induced a polarization potential, indicating K+ leakage, but no movement of cations and anions was allowed until AmB concentrations greater than 0.1 μm were added. In agreement with these data, it was found that AmB altered the negative membrane potential held across LPs in
a manner consistent with the differential cation/anion selectivity exhibited by the channels formed in liposomes. Thus, LPs
suspended in an iso-osmotic sucrose solution did not exhibit any AmB-induced membrane depolarization effect brought about
by efflux of anions until 0.1 μm or higher AmB concentrations were added. By contrast, LPs suspended in an iso-osmotic NaCl solution and exposed to 0.05 μm AmB exhibited a nearly total collapse of the negative membrane potential, indicating Na+ entry into the cells.
The concentration dependence of the AmB-induced permeability to different salts was also measured across vesicles derived
from the plasma membrane of leishmanias (LMVs), by using a rapid mixing technique. At concentrations above 0.1 μm, AmB induced the formation of aqueous pores across LMVs with a positive cooperativity, yielding Hill coefficients between
2 to 3. Measured anion selectivity across such aqueous pores followed the sequence: SCN > NO3 > Cl > I > Br > acetate (SO2−
4 being impermeable). Cell killing by AmB was followed by fluorescence changes of the DNA-binding compound ethidium bromide
(EB). At low concentrations (≤0.1 μm), AmB was found to be nonlethal against LPs but, above this concentration, leishmanias were rapidly killed. The rate and
extent of such an effect were found to be dependent on the type of cation and anion present in the external aqueous solution.
For both NH+
4 and Na+ salts, the measured rank order of AmB cell killing followed the same sequence that was determined for AmB-induced salt permeation
across LMVs. Further, replacement of either extracellular Na+ by choline or Cl− by SO2−
4, or its partial substitution by sucrose, in iso-osmotic conditions, led to a complete inhibition of the killing effect exerted
by otherwise lethal AmB concentrations. Finally, it was shown that tetraethylammonium (TEA+), an organic cation that is known to block AmB-induced salt permeation across LMVs was able to retard the time lag observed
for EB incorporation across LPs, indicating that this parameter can be taken to represent the time taken for salt accumulation
inside the parasites. The present results thus indicate clearly that low AmB concentrations (≤0.1 μm) were able to form across LPs, cation channels that collapsed the parasite membrane potential but are not lytic. At high
concentrations (<≥0.1 μm), a salt influx via the aqueous pores formed by the antibiotic was followed by osmotic changes leading to cell lysis. This
last stage is supported by electron microscopy observations of the changes of parasite morphology immediately upon addition
of AmB, which indicated that the typical elongated promastigote cell forms became rounded and the flagella swells and round
up. The present work is the first demonstration of the in vitro sensitivity of Leishmania promastigotes to osmotic lysis by AmB.
Received: 25 September 1995/Revised: 11 March 1996 相似文献