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1.
Narrow concentration intervals were used, covering 10?6– 10?4M desaspidin. The interaction with glycolysis involves three steps, the inhibitor constants (Ki:s) being in turn 2.7 × 10?5M, 1.3 × 10?4M, and high. About 18% of total glycolysis is inhibited in each of the two first steps, and 65% left for the third reaction. After compensation for glycolysis, oxidative phosphorylation may show a sudden jump to about 10% inhibition at 1.5 × 10?5M desaspidin, the possible Ki of the reaction starting here being very high. Correcting for glycolysis, desaspidin affects total Photophosphorylation in two steps, with the Ki values of 7.8 × 10?5M and 4.6 × 10?4M respectively. Inhibition in the first step is about 27% of the total photophosphorylation. By applying 10?6M DCMU[/3-(3, 4-dichlorophenyl)-l, l-dimethy lurea], one can abolish non-cyclic photophosphorylation. Desaspidin then reacts in a single step with a Ki of 1.4 × 10?4M. At 5 × 10?5M DCMU, also the pseudocyclic photophosphorylation is abolished. The remaining, true cyclic photophosphorylation has a single Ki of 2.3 × 10?5M for desaspidin. Under non-cyclic conditions, the true cyclic process contributes about 25% to total Photophosphorylation. Under pseudocyclic conditions, no cyclic photophosphorylation occurs. Under true cyclic conditions, the non-cyclic and pseudocyclic processes are inoperative. This indicates a regulative system, so that either (1) the (non-cyclic + true cyclic), (2) only the pseudocyclic, or (3) only the true cyclic systems can be traced, dependent on the level of DCMU applied. There are two sites for non-cyclic Photophosphorylation, one of them common to the pseudocyclic pathway. Cyclic photophosphorylation has a third site, different from the other two.  相似文献   

2.
Several new 10-formyl and 10-hydroxymethyl derivatives of 5,8,10-trideazapteroic acid have been synthesized by a novel and convenient enamine alkylation procedure. Two of these compounds (10a and 10b) were shown to be very powerful inhibitors of L. casei (10a, IC50 = 8 × 10−6 M ; 10b, IC50 = 7 × 10−6 M ) and recombinant mouse (10a, IC50 = 3.4 × 10−5 M ; 10b, IC50 = 2.8 × 10−5 M ) glycinamide ribonucleotide formyltransferase (GARFT). These IC50 values are comparable to the classical GARFT inhibitor (6R)-DDATHF (IC50, L. casei 2.3 × 10−6M ; recombinant mouse 2.3 × 10−5 M ) under identical assay conditions. For both compounds, the inhibition of L. casei GARFT increased with time of incubation, but not markedly with the recombinant mouse enzyme. Due to their potential ability to interfere with purine biosynthesis and to penetrate microbial cells the new nonclassical GARFT inhibitors reported here may be useful for the treatment of infections caused by microorganisms that are sensitive and resistant to conventional antimicrobial agents.  相似文献   

3.
An extracellular 45 kDa endochitosanase was purified and characterized from the culture supernatant of Bacillus sp. P16. The purified enzyme showed an optimum pH of 5.5 and optimum temperature of 60°C, and was stable between pH 4.5-10.0 and under 50°C. The K m and V max were measured with a chitosan of a D.A. of 20.2% as 0.52 mg/ml and 7.71×10?6 mol/sec/mg protein, respectively. The enzyme did not degrade chitin, cellulose, or starch. The chitosanase digested partially N-acetylated chitosans, with maximum activity for 15-30% and lesser activity for 0-15% acetylated chitosan. The chitosanase rapidly reduced the viscosity of chitosan solutions at a very early stage of reaction, suggesting the endotype of cleavage in polymeric chitosan chains. The chitosanase hydrolyzed (GlcN)7 in an endo-splitting manner producing a mixture of (GlcN)2-5. Time course studies showed a decrease in the rate of substrate degradation from (GlcN)7 to (GlcN)6 to (GlcN)5, as indicated by the apparent first order rate constants, k 1 values, of 4.98×10?4, 2.3×10?4, and 9.3×10?6 sec?1, respectively. The enzyme hardly catalyzed degradation of chitooligomers smaller than the pentamer.  相似文献   

4.
SYNOPSIS. Paramecium multimicronucleatum was exposed to various external concentrations of adenosine triphosphate (Na2ATP) to determine the effects thereof on the cycling rate of the nephridial apparatus. Normal rate was found to vary from 3.46 to 4.28 cycles/min with a mean rate of 3.85 cycles/min at 20 C. Concentrations of ATP of less than 5 × 10−4 M caused only slight, very temporary acceleration of the cycling rate. At 5 × 10−4 M the cycling rate was accelerated less than 15%. At 3 × 10−3 M cycling rate was accelerated, varying from 5.35 to 7.24 cycles/min, with a mean accelerated rate of 6.25 cycles/min, a mean aoceleration of 88.3%. Changes in rate after addition of 5 × 10−3 M ATP ranged from a decrease of 6.2% to an increase of 1.8%, with the nephridial apparatus ultimately stopping. At higher concentrations, stoppage was almost immediate. Paramecium is rapidly dehydrated by the ATP-accelerated cycling of its nephridial apparatuses, with a net loss of 27% of its volume in 6 minutes in the 3 × 10−3 M ATP.  相似文献   

5.
—The hydrolysis of ThTP by rat brain membrane-bound ThTPase is inhibited by nucleoside diphosphates and triphosphates. ATP and ADP are most effective, reducing hydrolysis by 50% at concentrations of 2 × 10?5m and 7·5 × 10?5m respectively. Nucleoside monophosphates and free nuclcosides as well as Pi have no effect on enzyme activity. ThMP and ThDP also fail to inhibit hydrolysis in concentrations up to 5 × 10?3m . Non-hydrolysable methylene phosphate analogs of ATP and ADP were used in further kinetic studies with the ThTPase. The mechanism of inhibition by these analogs is shown to be of mixed non-competitive nature for both compounds. An observed Ki, of 4 × 10?5m for the ATP analog adenosine-PPCP and 9 × 10?5m for the ADP analog adenosine-PCP is calculated at pH 6·5. Formation of the true enzyme substrate, the [Mg2+. ThTP] complex, is not significantly affected by concentrations of analogs producing maximal (>95%) inhibition of enzyme activity. Likewise the relationships between pH and observed Km and pH and Vmax are not shifted by the presence of similar concentrations of inhibitor.  相似文献   

6.
Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10−5) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty = 1 × 10−15, pfrailty = 2 × 10−19), transgelin (TAGLN; pprefrailty = 2 × 10−12, pfrailty = 6 × 10−22), and insulin-like growth factor-binding protein 2 (IGFBP2; pprefrailty = 5 × 10−15, pfrailty = 1 × 10−15) and with a lower level of growth hormone receptor (GHR, pprefrailty = 3 × 10−16, pfrailty = 2 × 10−18). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10−5). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty-acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.  相似文献   

7.
It is now well established that the size distribution of phytoplankton plays an important role in primary production processes and nutrient dynamics of coastal environment. In situ observations showed that nanophytoplankton (3–20 μm) contributed 72.08% and58.18% of phytoplankton biomass and 58.32% and 41.14% of primary productivity to Xiamen Western Waters and the northern Taiwan Strait, respectively; picophytoplankton (0.2–3 μm) dominated the biomass (64.70%) and productivity (66.09%) in the southern Taiwan Strait. Furthermore, nanophytoplankton accounted for 75% of phosphate uptake with the highest rate constant (8.3×10-5 s-1) and uptake rate in unit water volume (5.4×10-5 mmol dm-3s-1); picophytoplankton had the highest uptake rate in unit biomass (5.4×10-5 mmol mg-1s-1) and photosynthetic index (3.8 mgC mgChl a-1h-1). All the results highlighted the remarkable characteristics of small size ranged (0.2–20 μm) phytoplankton in subtropical coastal environments: main contributor to phytoplankton biomass and production, high efficiency on organic carbon production and nutrient recycling. The far reaching environmental and ecological implications were discussed. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   

8.
Abstract

Bacterial symbionts are one of the most toxic bacteria to insect pests. They have been isolated from the intestine of the entomopathogenic nematodes. Ten strains of the entomopathogenic nematodes, that may be different, have been isolated out of different soil fauna having different crops from different Governorates in Egypt. The bacterial symbionts in these strains have been isolated and tested for production parameters using four different media. Experiments showed that both Loria Broth (LB), and Nutrient Broth (NB) gave good results in laboratory production of bacterial symbionts, concerning stability, cell size, and pigment production during culturing. Experiments using different techniques of introducing the bacterial symbionts to larvae of the cotton leafworm showed that the injection technique was the most effective among all the tested techniques. This is followed by oral and forced feeding which seemed to give equal results. On the other hand, toxicity experiments showed that the four bacterial isolates named, G-NRC-A3, SH-NRC-A5, SH-NRC-A6, and N.Sinai-NRC-A8, besides the bacterial symbiont of Steinernema abbasi, Flavimonas oryzihabitans, all give 100% mortalities to Spodoptera littoralis larvae after 24 h post-treatment at the higher dose (5×104 cells/10 μl) but at the lower doses 5×103 and 5×102 cells/10 μl of injection solution, a 100% mortality was reached after 72 h post-treatment.  相似文献   

9.
The pathogenicity and virulence of 10 isolates of entomopathogenic fungi from the soil of lodging pens of dairy production units in Aguascalientes, Mexico, on adults of Stomoxys calcitrans and Musca domestica were determined. All isolates were pathogenic when exposed by aspersion to a concentration of 1×108 conidia/ml, causing between 20.3 and 91.7% mortality in S. calcitrans and between 31 and 91.7% in M. domestica at 7 days post-exposure; in S. calcitrans isolates of Beauveria bassiana (Bb114) and Metarhizium anisopliae (Ma135), sensu lato, were the most noteworthy as mortality reached above 90% with an LC50 of 3.5×105 conidia/ml for Bb114, while for Ma135 reached 1.6×104 conidia/ml. In M. domestica Ma134 and Ma135 showed mortality above 90% with an LC50 of 4.3×104 and 1.4×105 conidia/ml, respectively.  相似文献   

10.
Antonospora locustae is a microsporidian parasite of grasshopper insects that is used as a biological control agent. We report on laboratory selection of isolates from different regions with increased virulence. Bioassays were conducted against third instar nymphs of Locusta migratoria manilensis. AL2008L01 was originally imported from the USA in 1986, AL2008M01 was isolated from Melanoplus differentialis in USA and AL2008F01 was isolated from infected Fruhstorferiola tonkinensi collected in Guangdong, China. The results showed that all three isolates can infect the locust and that pathogenicity increased gradually with increased dose. The LD50 values of the original isolates at the highest dose (5×106 spores/nymph) were 19, 23 and 22 days and LD50 values were 3.2×105, 3.4×106 and 0.7×106 spores/g, respectively. After selecting for three generations, the virulence of all isolates increased significantly. LT50s were reduced to 17, 20 and 21 days at the highest dose (5×106 spores/nymph) and LD50s were reduced to 1.4×105, 2.5×105 and 1.7×105 spores/g.  相似文献   

11.
The pathogenicity of Beauveria bassiana to one of the major pests of citrus crops, Phyllocoptruta oleivora, was assessed by inoculating mites with different concentrations of conidia (1×106, 5×106, 1×107, 5×107 and 1×108). Treated mites were kept at controlled conditions (25 ± 0.5°C, 12 h photoperiod and 98% relative humidity) and mite survivorship was evaluated daily. Mortality was found to increase in time and was dependent on the conidia concentration, with values ranging from 24 to 91% for the lowest and highest conidia concentration, respectively. The calculated LC50 on the fifth day was 4.23×106 conidia/ml. Mean lethal time was 3.98, 9.79, 3.09 and 2.74 days for 5×106, 1×107, 5×107 and 1×108 conidia/ml, respectively. Conidia were found to adhere all over the mite body surface, especially at the anal region, where vegetative mycelium was found entering the mite body. We noticed the formation of small crystals inside the mite’s body that were produced during colonization of the body cavity by the fungus. This is the first report of B. bassiana pathogenicity for this species.  相似文献   

12.
Aims: To optimize the transformation conditions and improve the transformation efficiency of Bacillus subtilis WB800 and DB104. Methods and Results: Trehalose, which could decrease the damage of electric shock to the cells, was added to the electroporation medium containing sorbitol and mannitol. The factors affecting the transformation efficiency, such as the growth phase of bacteria, cell concentration, electric field strength and plasmid variety, were examined and improved. The new method increased the transformation efficiency of B. subtilis by nearly 100‐fold compared with the conventional one. Conclusions: With the optimized method, the transformation efficiency came up to 3·64 × 105 transformants μg?1 DNA for WB800, and 2·10 × 105 transformants μg?1 DNA for DB104. Significance and Impact of the Study: This improvement in transformation efficiency will be largely attributed to the research of expression of exogenous genes in B. subtilis, gene library construction for directed evolution and transformation of wild‐type B. subtilis strains.  相似文献   

13.
A sampling method is described to determine accurately the number of fast myotomal muscle fibres (NF) in a large flatfish species, the Atlantic halibut Hippoglossus hippoglossus. An unusual feature of the fast myotomal muscle is the presence of internalized strips of slow muscle fibres. In fish of 1·5–3·5 kg (n = 24), the total cross‐sectional area (ATC) of fast muscle was 18% greater in the dorsal than ventral myotomal compartments (P < 0·05), whereas there was no significant difference between left‐ and right‐hand sides of the body. Due the bilateral asymmetry, muscle blocks (5 × 5 × 5 mm) were prepared to systematically sample each myotomal quadrant (dorsal, ventral, left‐ and right‐side) and the diameters of 150 fast fibres measured per block. Smooth non‐parametric probability functions were fitted to a minimum of 800 measurements of fibre diameter per quadrant (n = 5). There were no significant differences in the distribution of muscle fibre diameters between myotomal compartments and therefore NF could be estimated from a single quadrant. The number of blocks required to estimate NF with a repeatability of ±2·5% increased from six at 300 g body mass to 17 at 96·5 kg, caused by variation within and between blocks. Gompertz curves were fitted to measurements of fibre number and fork length (LF). The estimated final fibre number was 8·96 × 105 (7·99–9·94 × 105, 95% CI) for males and 1·73 × 106 (1·56–1·90 × 106, 95% CI) for female fish. The estimated LF for cessation of fibre recruitment in the fast muscle of female fish (1775 mm) was almost twice that in males (810 mm), reflecting their greater ultimate body size.  相似文献   

14.
Bacterial dynamics in two high-arctic lakes   总被引:1,自引:0,他引:1  
The heterotrophic planktonic bacteria in two high-arctic lakes were studied by direct microscope count and the enzymatic uptake of 14C labelled glucose which generally conformed to Michaelis-Menten kinetics. Bacterial numbers and activity in oligo-trophic Char Lake ranged from 0.1 to 2.0×10?3 bacteria/l and a maximum uptake velocity (Vmax) of 1.8 × 10?3μg glucose l? h?1. Nearby Meretta Lake received waste water from the Department of Transport Base at Resolute and this eutrophication was reflected in higher bacterial numbers of 2-80 × 108/1 and Kmax of 0.1 × 10?1-7.5 × 10?1 fig glucose l?1 h?1 The Kmax per cell in Char Lake was 3 × 10?11μg glucose l?1 h?1 and changed little between the period of solid ice cover in May and ice-free conditions in August. Bacterial cycles could not be related to phytoplankton cycles in either lake. Comparison of kinetic data from several lakes suggests a relationship between the bacterial uptake rate of glucose and phytoplankton production. Both bacterial numbers and activity in Char Lake may be very close to the minima to be expected in undisturbed freshwater environments.  相似文献   

15.
Uptake and assimilation of nitrogen and phosphorus were studied in Olisthodiscus luteus Carter. A diel periodicity in nitrate reductase activity was observed in log and stationary phase cultures; there was a 10-fold difference in magnitude between maximum and minimum rates, but other cellular features such as chlorophyll a, carbon, nitrogen, C:N ratio (atoms) · cell?1 were less variable. Ks values (~2 μM) for uptake of nitrate-N and ammonium-N were observed. Phosphorus assimilated · cell?1· day?1 varied with declining external phosphorus concentrations; growth rates <0.5 divisions · day?1 were common at <0.5 μM PO4-P. Phosphate uptake rates (Ks= 1.0–1.98 μM) varied with culture age and showed multiphasic kinetic features. Alkaline phosphatase activity was not detected. Comparisons of the nutrient dynamics of O. luteus to other phytoplankton species and the ecological implications as related to the phytoplankton community of Narragansett Bay (Rhode Island) are discussed.  相似文献   

16.
R. J. Milner 《BioControl》1973,18(3):305-315
The pathogenicity ofNosema whitei was studied using a dose-mortality technique; larvae ofTribolium castaneum were reared for the duration of each experiment in flour mixed with known numbers of spores. The susceptibility of each of the first 5 larval instars was compared. The LD50 (for mortality after 20 days) increased consistently from the first instar (1.8×106 spores/g) to the fifth instar (1.0×1010 spores/g). The slopes of the probit lines increased consistently as age increased (from b=1.1 to b=3.9). Two factors which reduce the development time ofT. castaneum, high temperature and high humidity, both reduced the pathogenicity ofN. whitei. Thus pathogenicity decreased as the temperature was increased fram 25°C (LD50=4.2×106) through 30°C (LD50=1.3×107) to 35°C (LD50=3.2×106), also pathogenicity decreased consistently as humidity was increased fram 10%, through 30, 50, 70% to 90% R.H. Adults, emerging fromNosema free larvae, became infected only when exposed to a very high dose (2×1010 spores/g for 14 days from the day of emergence). Infected larvae were treated for 1 hr. at 45°C in an attempt to cure the infection. The infected larvae were not cured, rather the treatment had an adverse alfect on their survival.
Résumé La pathogénicité deNosema whitei a été étudiée en élevant des larves deT. castaneum dans de la farine mélangée à des quantités connues de spores. La sensibilité des larves diminue uniformément en fonction de l'age; La DL50 varie de 1,8×106/g (1er stade) à 1,0×1010 spores/g (5e stade). Deux facteurs, qui accélèrent le développement deT. castaneum, des températures et des humidités élevées, réduisent tous les deux la pathogénicité deN. whitei. Les adultes ne peuvent être infectés qu'en les exposant à la dose extrêmement élevée de 2×1010 spores/g. Un traitement par la chaleur (45°C pendant une heure) n'a pas réussi à guérir les larves.


This work financed by a Science Research Council (U.K.) studentship is based on a thesis submitted for a degree of Ph. D. at the University of Newcastle-upon-Tyne.  相似文献   

17.
The frequency of algal blooms has increased in the mid and downstream reaches of the Xiangjiang River (Hunan, China), one of the most heavily polluted rivers in China. We identified the bloom-forming species in a bloom that occurred mid-late September 2010. In addition, we determined the extent of metal bioaccumulation in the algae and measured the toxicity of the algae using a mouse bioassay. Water samples were collected at upstream (Yongzhou), midstream (Hengyang), and downstream (Zhuzhou, Xiangtan, and Changsha) sites. The dominant species was Aulacoseira granulata, formerly known as Melosira granulata. The heaviest bloom occurred at Xiangtan and Changsha, where the number of A. granulata peaked at 1.3×105 filaments L−1 and chlorophyll a at 0.04 mg L−1. Concentrations of Al, Fe, and Mn were 4.4×103, 768.4, and 138.7 mg kg−1 dry weight in the phytoplankton. The bioaccumulation factor was 4.0×105, 7.7×105, and 3.2×103, respectively. The heavy metal Pb had the greatest tendency to bioaccumulate among the highly toxic heavy metals, with a concentration of 19.2 mg kg−1 dry weight and bioaccumulation factor of 9.6×103. The mouse bioassay suggested the bloom was toxic. The LD50 was 384 mg kg−1 and all surviving mice lost weight during the first 72 h after exposure. Our results demonstrate that blooms of A. granulata in rivers contaminated with heavy metals pose a threat to freshwater ecosystems and human health. Thus, measures should be taken to control eutrophication and heavy metal pollution in such rivers.  相似文献   

18.
Outbreak of blue-green algal blooms, with associated unsightly scum and unpleasant odor, occurs frequently in eutrophic lakes. We conducted feeding experiments to study ingestion and digestion of Microcystis aeruginosa by tilapia (Oreochromis niloticus) under laboratory conditions and field testing to reduce Microcystis blooms by stocking tilapia in Lake Yuehu and other eutrophic waters in Ningbo, China between 2000 and 2003. Our results show that tilapia was capable of ingesting and digesting a large quantity of Microcystis. Digestion efficiency ranged from 58.6 to 78.1% at water temperature of 25 °C. Ingestion rate increased with increasing fish weight and water temperature. Intensive blooms occurred in Lake Yuehu in both 1999 and 2000. The lake was stocked with silver carp (Hypophthalmichthys molitrix), bighead (Aristichthys nobilis) and a freshwater mussel (Hyriopsis cumingii) at a total biomass of 9.8 g m−3 in early 2001, and tilapia at 3–5 g m−3 in April of 2002. From June to October, average phytoplankton density decreased from 897.6×106 cells l−1 in 2000 to 291.7×106 cells l−1 in 2001 and 183.0×106 cells l−1 in 2002. Compared to 2000, the annual average phytoplankton biomass in 2001 and 2002 decreased by 48.6% and 63.8%, respectively. The blue-green algal biomass which made up 70% of the total phytoplankton biomass in 2000 was reduced to 22.1% in 2001 and 11.2% in 2002. Meanwhile, Secchi depth increased from 20–50 cm to 55–137 cm during the same time period. Similar results were observed in some other eutrophic waters. For example, algal bloom disappeared about 20 days after tilapia fingerlings were stocked (8–15 g m−3) to a pond in Zhenhai Park. Chlorophyll a concentration and phytoplankton production declined dramatically whereas water transparency increased substantially. However, the impacts of tilapia on nitrogen and phosphorus dynamics in natural lakes need further investigation. Our studies revealed that stocking tilapia is an effective way to control algal blooms in eutrophic waters, especially in lakes where nutrient loading cannot be reduced sufficiently, and where grazing by zooplankton cannot control phytoplankton production effectively.  相似文献   

19.
The synthesis and antioxidant evaluation of some novel benzimidazole derivatives (1024) are described. Antioxidant properties of the compounds were investigated employing various in vitro systems viz., microsomal NADPH-dependent inhibition of lipid peroxidation (LP), interaction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and scavenging of superoxide anion radical. Compounds 12 and 13 showed very good antioxidant capacity and were 17–18 -fold more potent than BHT (IC50 2.3 × 10? 4M) with 1.3 × 10? 5M and 1.2 × 10? 5M IC50 values, respectively, by interaction of the stable DPPH free radical.  相似文献   

20.
Abstract: Pridefine (AHR-1118) is a pyrrolidine derivative with clinically established antidepressant efficacy. Previous work from this laboratory indicates that pridefine is a reuptake blocker of catecholamines and serotonin with weak releasing activity. This study characterized the mode of amine uptake inhibition by pridefine as noncompetitive. The uptake experiments were performed utilizing ouabain instead of zero-degree controls to differentiate between the passive and active components of uptake. Furthermore, the passive component was resolved into diffusion and binding of substrate. Correction was made for the effects of ouabain on binding. Kinetic constants determined from Lineweaver-Burk plots were: Km= 3 × 10?7 M for NE, Km= 9 × 10?8 M for DA, and Km= 3 × 10?8 M for 5-HT. Dixon analyses of uptake at various pridefine concentrations indicated noncompetitive inhibition with Ki= 2.5 × 10?6 M for NE uptake, Ki= 2.0 × 10?6 M for DA uptake, and Ki= 1 × 10?5 M for 5-HT uptake. These constants compare well with IC50 values for the same transmitters: NE, IC50= 2.4 × 10?6 M; DA, IC50= 2.8 × 10?6 M; 5-HT, IC50= 1.0 × 10?5 M. The in vitro results indicate that pridefine is relatively specific as a catecholamine uptake blocker. It differs from tricyclic antidepressants which are reportedly competitive inhibitors of monoamine uptake. The possible mechanisms by which pridefine acts as a noncompetitive inhibitor are discussed.  相似文献   

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