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1.
Prostaglandins (PG) of both the E and F series may serve as modulators of norepinephrine (NE) release from peripheral sympathetic neurons. We have studied the effects of PGE2 and PGF on the accumulation and release of 3H-NE in the CNS using synaptosomes isolated from rat hypothalami.The release of 3H-NE from synaptosomes superfused with Krebs-Ringer bicarbonate buffer was multiphasic with an initial fast release phase followed by a slower release. Raising KC1 concentration of the superfusion medium to 56mM during the slow release phase is known to stimulate 3H-NE release. PGE2 (1 × 10?6M) attenuated 3H-NE release during the fast phase and reduced the amount of 3H-NE released due to KC1 stimulation. At lower concentrations of PGE2 there was no change in the release profile. PGF was without effect on 3H-NE release at all concentrations tested.The accumulation of 3H-NE was significantly diminished by PGE2 at a concentration of 1 × 10?6M, while a lower concentration (1 × 10?7M) was ineffective. PGF had no effect on 3H-NE accumulation at all concentrations investigated.  相似文献   

2.
Two hundred sixty-four δ18O and δ13C values of Permian articulate brachiopod shells were analyzed and 81 of these values were characterized as well preserved and biostratigraphically well defined. These were then utilized for construction of baseline oxygen and carbon isotope curves for the Permian interval. In addition, 21 δ13C whole rock values are reported for the Wordian and Capitanian.The early Permian, Asselian to Artinskian, times are characterized by ∼ 2.5‰ decrease in oxygen isotope values, from ∼ − 0.7‰ to − 3.3‰ (V-PDB). This is attributed to a ∼ 4-7 °C increase in temperature in the Southern Urals, concomitant with the retreat of the Permo-Carboniferous ice sheets and return of the 18O-depleted melt water into the oceans. The Late Permian samples from Iran (Jolfa at Kuh-e-Ali-Bashi) and China (Meishan) yield δ18O values, and presumably temperatures, similar to those that followed the termination of the large-scale glaciation in the Lower Permian. In between, the upper Kungurian to Capitanian samples from the Delaware Basin (Guadalupe Mountains) are enriched in 18O, at − 1.5‰ to − 3‰. We have no definitive explanation for these data, but tentatively suggest that the “anomaly” can potentially be a result of evaporative enrichment of seawater in 18O, due to intracratonic arid setting of the basin. The 18O-enriched nature of the Zechstein samples (− 1.2‰ to + 2.5‰), on the other hand, is in all probability a reflection of the high evaporation rates in the Zechstein sea.The Permian interval is characterized by a relatively constant δ13C, at about 4‰. The exceptions are again the brachiopods from the Delaware Basin (Guadalupe Mountains), which show ∼ 1.6‰ increase in the Guadalupian, to values of up to 5.9‰ in the Wordian. A tentative explanation, as in the case of oxygen, is based on the proposition that the semi-enclosed Delaware Basin was likely stratified, with sequestration of the 13C-depleted carbon to the deeper water layers and a complementary 13C enrichment in the upper oxygenated layer. The coeval open ocean water DIC may have been similar to that of the remainder of the Permian interval, at ∼ 4‰, as indicated by whole rock carbonate samples from Oman, Sicily, and Iran. In the latest Permian, the trend mimics the well-known δ13C drop at the Permian/Triassic boundary.  相似文献   

3.
Preliminary experiments suggested that total levels of radioactivity disappeared from the blood of male, Fischer rats much more rapidly following intragastric administration of 14C-Δ9-tetrahydrocannabinol (14C-THC) than 3H-THC. Collaborative experiments at the Stanford Research Institute (SRI) and the Research Institute on Alcoholism (RIA) verified and characterized the initial observations. In rats that had food available throughout the experiments, the concentrations of total 3H and 14C in fresh plasma reached a maximum at 2 – 4 hours after treatment with 3H-THC plus 14C-THC. Thereafter, 14C levels fell while 3H levels decreased very slowly or not at all. In fasted rats, peak plasma concentrations of both isotopes were not attained until about 8 hours following drug administration. The concentrations of 14C then decreased more rapidly than 3H. The differences between the plasma disappearance curves for 14C and 3H were not dependent upon the method of blood collection or the techniques of isotope counting. However, when plasma or whole blood samples were dried before radioisotope analysis, the difference between 14C and 3H concentrations was virtually abolished in fed and fasted rats. Experiments suggest that tritiated water, produced during the metabolism of 3H-THC, may be responsible for the prolonged maintenance of high 3H levels in the blood.  相似文献   

4.
In the present study, (3aR,7aS)-1,3,3a,4,7,7a-hexahydroisobenzofuran was submitted to photooxygenation and two isomeric hydroperoxides were successfully obtained. Without any further purification, reduction of the hydroperoxides with titanium tetraisopropoxide catalyzed by dimethyl sulfide gave two alcohol isomers in high yields. After acetylation of alcohol with Ac2O in pyridine, epoxidation reaction of formed monoacetates with m-CPBA, then chromatographed and followed by hydrolysis of the acetate groups with NH3 in CH3OH resulted in the formation of epoxy alcohol isomers respectively. These epoxy alcohol isomers were subjected to trans-dihydroxylation reaction with acid (H2SO4) in the presence of water to afford triols. Acetylation of the free hydroxyl groups produced benzofuran triacetates in high yields. Ring-opening reaction of furan triacetates with sulfamic acid catalyzed in the presence of acetic acid/acetic anhydrate and subsequently hydrolysis of the acetate groups with ammonia gave the targeted cyclohexane carbasugar-based pentols. All products were separated and purified by chromatographic and crystallographic methods. Structural analyses of all compounds were conducted by spectral techniques including NMR and X-ray analyses. The biological inhibition activity of the target compounds was tested against glycosidase enzymes, α- and β-glucosidase.  相似文献   

5.
6.
β2-GlycoproteinI was shown to be a hydrophilic protein exhibiting no charge shift in the presence of a cationic detergent, but a charge shift in the presence of an anionic detergent. The latter was suggested to be caused by a binding of β2-glycoprotein I to deoxycholate in the Triton X-100/deoxycholate micelles. Quantification by electroimmunoassay of asialo-β2-glycoprotein and I and subfractions of β2-glycoprotein I gave different results although identical results were obtained in single radial immunodiffusion. Addition of 0.2% (w/v) of deoxycholate to the agarose gels containing Triton X-100 prior to electrophoresis, however, eliminated these differences. The effect of deoxycholate on the rate of migration of β2-glycoprotein I was found applicable for electroimmunoassay of the protein. Crossed immunofocusing of plasma from individual donors, electrophoresed in an agarose containing Triton X-100/deoxycholate micelles confirmed a postulated variation in the relative composition of subfractions of β2-glycoprotein I in plasma earlier suggested by Finlayson and Mushinski (Finlayson, J.S. and Mushinski, J.F. (1967) Biochim. Biophys. Acta 147, 413–420).  相似文献   

7.
Our previously published prostaglandin (PG) synthesis route, in which the ω-chain is added in the penultimate step, provides facile access to a wide variety of ω-chain variant PG analogs. Each series requires only the synthesis of the appropriate methylated acylphosphonate for the Emmons' condensation. The syntheses of analogs bearing the following methylation pattern are detailed: 15-Me; 17, 17-(Me)2; 17, 17, 20-(Me)3; 18, 18, 20-(Me)3; 15, 18, 18, 20-(Me)4; and 15-Ome-18, 18, 20-(Me)3. The well-known 16, 16-dimethyl prostaglandins have also been prepared by this sequence. The synthesis of 16, 16-tetramethylene-PG analogs is also described.  相似文献   

8.
Rotation of the γ subunit of the F1-ATPase plays an essential role in energy transduction by F1-ATPase. Hydrolysis of an ATP molecule induces a 120° step rotation that consists of an 80° substep and 40° substep. ATP binding together with ADP release causes the first 80° step rotation. Thus, nucleotide binding is very important for rotation and energy transduction by F1-ATPase. In this study, we introduced a βY341W mutation as an optical probe for nucleotide binding to catalytic sites, and a βE190Q mutation that suppresses the hydrolysis of nucleoside triphosphate (NTP). Using a mutant monomeric βY341W subunit and a mutant α3β3γ subcomplex containing the βY341W mutation with or without an additional βE190Q mutation, we examined the binding of various NTPs (i.e., ATP, GTP, and ITP) and nucleoside diphosphates (NDPs, i.e., ADP, GDP, and IDP). The affinity (1/Kd) of the nucleotides for the isolated β subunit and third catalytic site in the subcomplex was in the order ATP/ADP > GTP/GDP > ITP/IDP. We performed van’t Hoff analyses to obtain the thermodynamic parameters of nucleotide binding. For the isolated β subunit, NDPs and NTPs with the same base moiety exhibited similar ΔH0 and ΔG0 values at 25°C. The binding of nucleotides with different bases to the isolated β subunit resulted in different entropy changes. Interestingly, NDP binding to the α3β(Y341W)3γ subcomplex had similar Kd and ΔG0 values as binding to the isolated β(Y341W) subunit, but the contributions of the enthalpy term and the entropy term were very different. We discuss these results in terms of the change in the tightness of the subunit packing, which reduces the excluded volume between subunits and increases water entropy.  相似文献   

9.
The potentials of a series of one-electron oxidation and reduction reactions have been determined for manganese group half-sandwich complexes of the tricarbadecaboranyl ligand PhC3B7H9 and the penta-organo fullerene ligand C60Bn2PhH2 (Bn = benzyl). The anodic processes were studied in CH2Cl2 and the cathodic processes were studied in both CH2Cl2 and THF, the supporting electrolyte being [NBu4][B(C6F5)4]. The manganese complex Mn(CO)2(PMe3)(PhC3B7H9) (1) is a member of a three-electron transfer series which includes oxidation to 1+ (0.51 V versus ferrocene) and successive reductions to 1 (−1.66 V) and 12− (−1.77 V). Both the oxidation and reduction of the closely-related complex Mn(CO)2(PPh3)(PhC3B7H9) (2) are chemically irreversible under slow-scan cyclic voltammetry conditions. The rhenium complex Re(CO)2(PPh3)(PhC3B7H9) (3) oxidizes (E1/2 = 0.82 V versus ferrocene) to a radical cation which, unlike its cyclopentadienyl analogue, shows no evidence of dimerization. Oxidation of the fullerene-based complex Re(CO)3(C60Bn2PhH2) is more facile than that of its cyclopentadienyl analogue, in contrast to previous findings in this class of metal-fullerene derivatives. An electrochemical ligand factor, EL, of 0.63 is calculated for the PhC3B7H9 ligand in manganese group half-sandwich complexes.  相似文献   

10.
α-Bungarotoxin has been labeled with [3H]pyridoxamine phosphate, by reaction with pyridoxal phosphate followed by reduction with sodium boro[3H]hydride. Specific activities of up to 27 Ci/mmol have been obtained. Mono- and dilabeled toxins bind irreversibly to the acetylcholine receptor from Torpedo electroplax, despite a change in isoelectric point from 9.2 for native toxin to 6.2 for dilabeled toxin. The 3H-labeled α-bungarotoxin is usable for over a year.  相似文献   

11.
The effects of PGD2, PGF and PGE1 were studied on the circular muscle of post-ovulatory rabbit oviducts in vitro. PGE1 inhibited spontaneous contractile activity. Lower concentrations of PGD2 and PGF were stimulatory and higher concentrations were inhibitory. Since PGD2 may be produced in the oviduct, any hypothesis concerning the role of prostaglandins in the control of oviductal motility and ovum transport should include PGD2 as well as PGFs and PGEs.  相似文献   

12.
Reaction at pH = 2.3 of the [Mo2O2S2(OH2)6]2+ aqua cation with the tetravacant ion [β-B-HAs2W8O31]7− leads to the formation of a red solid from which three mixed salts have been obtained as single crystals and characterized by X-ray diffraction analysis. Three mixed salts K-5a, RbNa-5b, DMACs-5c exhibit a similar molecular arrangement consisting in three {β-HAs2W9O34} subunits mutually linked by three {Mo2O2S2} groups. The triangular arrangement delimits a large open-cavity, lined on the periphery by three outer {As-OH} groups and closed at the bottom by a small hexagonal pocket formed by six terminal oxygen atoms. The central hexagonal cavity is filled either by a potassium, a rubidium or a cesium cation. The outer {As-OH} groups are pointed towards two directions labelled up and down, respectively. In K-6a the three {As-OH} bonds are in up configuration leading to the {up, up, up} isomer. The structure of RbNa-5b is rather consistent with the superposition of the two {up, up, up} and {down, up, up} isomers disordered over the same crystallographic site, while only the {down, up, up} isomer is present in DMACs-5c. In solution, 183W NMR characterization of 6a as sodium salt results in a complicated spectrum consistent with the simultaneous presence of the four isomers, {up, up, up}, {down, up, up}, {down, down, up} and {down, down, down}, respectively. 5a reacts with three equivalents of iodine to give CsNa-6 isolated as single crystals. In 6, four β-{AsW9O33} moieties are located at the corner of a super tetrahedron and are mutually connected by six {Mo2O2S2} linkers. The three outer {As-OH} groups can be selectively removed by iodine, this oxidation reaction consisting in fact in a deprotecting process permitting the extension of the arrangement from triangular to tetrahedral.  相似文献   

13.
14.
Under alkaline conditions and in the presence of reductant, NADH or NADPH, and molecular oxygen, hemin catalyzes the regiospecific para-hydroxylation of aniline to form p-aminophenol [P.A. Adams, D.A. Baldwin, and M.C. Berman, J. Chem. Soc. (Lond) Chem. Commun. 856 (1979); P.A. Adams and M.C. Berman, J. Inorg. Biochem.17, 1 (1982)]. The reaction has now been studied in the presence of H2O2 and alkyl hydroperoxides and in the absence of oxygen and reductant. Results indicate that the H2O2? and alkyl hydroperoxide-supported processes proceed via different mechanisms involving, on the one hand, the hydroperoxide anion (HO2?) and on the other, the undissociated alkyl hydroperoxide molecule (ROOH). The addition of superoxide dismutase to the reaction had no effect, unlike the NADH/O2 supported reaction where the enzyme completely inhibits reaction. Similarities between the hemin-mediated peroxide-supported reactions reported here, and the cytochrome P-450-mediated peroxide-supported reactions reinforce our earlier contentions that the alkaline hemin system appears to be a good model for the in vivo activation of oxygen by hemoproteins.  相似文献   

15.
Using homonuclear 1H NOESY spectra, with chemical shifts, 3JHNHα scalar couplings, residual dipolar couplings, and 1H-15N NOEs, we have optimized and validated the conformational ensembles of the amyloid-β 1–40 (Aβ40) and amyloid-β 1–42 (Aβ42) peptides generated by molecular dynamics simulations. We find that both peptides have a diverse set of secondary structure elements including turns, helices, and antiparallel and parallel β-strands. The most significant difference in the structural ensembles of the two peptides is the type of β-hairpins and β-strands they populate. We find that Aβ42 forms a major antiparallel β-hairpin involving the central hydrophobic cluster residues (16–21) with residues 29–36, compatible with known amyloid fibril forming regions, whereas Aβ40 forms an alternative but less populated antiparallel β-hairpin between the central hydrophobic cluster and residues 9–13, that sometimes forms a β-sheet by association with residues 35–37. Furthermore, we show that the two additional C-terminal residues of Aβ42, in particular Ile-41, directly control the differences in the β-strand content found between the Aβ40 and Aβ42 structural ensembles. Integrating the experimental and theoretical evidence accumulated over the last decade, it is now possible to present monomeric structural ensembles of Aβ40 and Aβ42 consistent with available information that produce a plausible molecular basis for why Aβ42 exhibits greater fibrillization rates than Aβ40.  相似文献   

16.
Potential food sources and dominant invertebrates and fishes were collected for the examination of variability in 13C/12C and 15N/14N to determine the sources of carbon available to consumers within a Western Australian Posidonia sinuosa-dominated seagrass bed. Autotrophs showed a wide distribution of δ13C values, with P. sinuosa at −11.3 ± 0.8‰ and macroalgae ranging from −16.6 to −31.7‰. This variation allowed us to successfully identify macroalgae as the main contributor of carbon to the trophic structure, although no distinction could be made between epiphytic macroalgae on seagrass, or allochthonous macroalgal sources. The range in δ15N ratios among potential food items at the trophic base was too small to make it useful as tracer of nitrogen flow pathways, but it consistently increased from macrophytes and detritus (4.1–6.8‰), to invertebrates (5.7–7.4‰) located near the middle of the food web, to fishes (8.3–11.9‰), with piscivorous species such as Leviprora inops generally having a higher 15N. δ13C of seston (−12.8‰) and sedimentary organic matter (−8.7‰) indicate that seagrass material is the main contributor to these two carbon pools, and that very little of it contributes to animal biomass.  相似文献   

17.
The C1 domains of classical and novel PKCs mediate their diacylglycerol-dependent translocation. Using fluorescence resonance energy transfer, we studied the contribution of different negatively charged phospholipids and diacylglycerols to membrane binding. Three different C1B domains of PKCs were studied (the classical γ, and the novel δ and ?), together with different lipid mixtures containing three types of acidic phospholipids and three types of activating diacylglycerols. The results show that C1Bγ and C1B? exhibit a higher affinity to bind to vesicles containing 1-palmitoyl-2-oleoyl-sn-phosphatidic acid, 1-palmitoyl-2-oleoyl-sn-phoshatidylserine, or 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol, with C1B? being the most relevant case because its affinity for POPA-containing vesicles increased by almost two orders of magnitude. When the effect of the diacylglycerol fatty acid composition on membrane binding was studied, the C1B? domain showed the highest binding affinity to membranes containing 1-stearoyl-oleoyl-sn-glycerol or 1,2-sn-dioleoylglycerol with POPA as the acidic phospholipid. Of the three diacylglycerols used in this study, 1,2-sn-dioleoylglycerol and 1-stearoyl-oleoyl-sn-glycerol showed the highest affinities for each isoenzyme, whereas 1,2-sn-dipalmitoylglycerol; showed the lowest affinity. DSC experiments showed this to be a consequence of the nonfluid conditions of 1,2-sn-dipalmitoylglycerol;-containing systems.  相似文献   

18.
Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the following three animal models: (1) ovariectomized rats, (2) mated rats treated post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepristone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF and PGE2).Antiestrogens administered alone to ovariectomized rats did not effect uterine PGE2 or PGF concentrations; whereas the combination of anordiol/mifepristone increased uterine PGF concentration, resulting in an increase in the PGF/PGE2 ratio.Mated rats were treated post-coitally for three consecutive days with anordiol, tamoxifen, estradiol and mifepristone alone and with the combination of anordiol/mifepristone and tamoxifen/mifepristone. An increase in uterine PGF concentrations and in the PGF/PGE2 ratio occurred only in anordiol/mifepristone treated group. A decrease in uterine PGE2 concentrations occurred in animals treated with anordiol, tamoxifen and estradiol, resulting in an increase in the PGF/PGE2 ratio.Anordiol (5.0 mg/kg/day) and mifepristone (4.0 mg/kg/day) alone and the combination of anordiol/mifepristone (2.5/1.0 mg/kg/day) administered to pregnant rats on days 7, 8 and 9 of pregnancy induced an increase in PGF levels without affecting uterine PGE2 concentration. The changes in uterine PGF concentrations induced by anordiol and the combination of anordiol/mifepristone resulted in an increase in the PGF/PGE2 ratio.The antiestrogens tested except for ICI 182780 possessed agonist activity when assayed by measuring their capacity to increase the uterine weights in ovariectomized rats. Also, ICI 182789 was the only antiestrogen that did not influence uterine PG concentrations. It can be concluded that ICI 182780 is the only “pure” antiestrogen among those tested.The present results show that antiestrogens and the combination of mifepristone plus anordiol at doses preventing implantation and terminating pregnancy increase uterine PGF and/or decrease PGE2 concentrations, resulting in an alteration of PGF/PGE2 ratio. These findings suggest that there exists a critical balance of PGF to PGE2 concentrations in the uterus required for the normal passage of fertilized ova through the oviduct, initiating implantation of the blastocysts, development of embryos, and maintenance of pregnancy.  相似文献   

19.
Both intact cortical tissue and isolated cortical cells from the adrenal gland of the rat were analyzed for 6-keto-PGF, the hydrolysis metabolite of PGI2, using high-performance liquid chromatography and gas chromatography-mass spectrometry. 6-Keto-PGF was present in both incubations of intact tissue and isolated cells of the adrenal cortex, at higher concentrations than either PGF or PGE2. Thus, the cortex does not depend upon vascular components for the synthesis of the PGI2 metabolite. Studies in vitro, using isolated cortical cells exposed to 6-keto-PGF (10?6-10?4M), show that this PG does not alter cAMP levels or steroidogenesis. Cells exposed to PGI2 (10?6-10?4M), however, show a concentration-dependent increase of up to 4-fold in the levels of cAMP without altering corticosterone production. ACTH (5–200 μU/ml) increased cAMP levels up to 14-fold, and corticosterone levels up to 6-fold, in isolated cells. ACTH plus PGI2 produced an additive increase in levels of cAMP, however, the steroidogenic response was equal to that elicited by ACTH alone. Adrenal glands of the rat perfused in situ with PGI2 showed a small decrease in corticosterone production, whereas ACTH greatly stimulated steroid release. Thus, while 6-keto-PGF is present in the rat adrenal cortex, its precursor, PGI2, is not a steroidogenic agent in this tissue although it does stimulate the accumulation of cAMP.  相似文献   

20.
The reactions of [Pt2(μ-S)2(PPh3)4] towards a range of palladium(II) complexes containing organometallic ligands (cyclopalladated N-donor ligands, η3-allyl, phenyl) have been explored, leading to the formation of a series of cationic, trinuclear sulfido-bridged aggregates containing {Pt2PdS2} cores. [Pt2(μ-S)2(PPh3)4] also reacts with the platinum(II) hydride complex trans-[PtHCl(PPh3)2] giving the adduct [Pt2(μ-S)2(PPh3)4PtH(PPh3)]+. X-ray crystal structure determinations on the complexes [Pt2(μ-S)2(PPh3)4PdPh(PPh3)]PF6 and [Pt2(μ-S)2(PPh3)4PtH(PPh3)]PF6 are reported, and show the expected bis μ3-sulfido aggregates with three square-planar metal centres.  相似文献   

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