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1.
The paper describes the effect of exogenous oestradiol and progesterone on noradrenalin (NA) content in the ovary, tuba uterina, uterus, and vagina, and on the morphological features of adrenergic nerves in these organs in sexually immature female pigs. 30 animals were used, of body weight 37 to 43 kg, and age 115 to 125 d. The animals were divided randomly into 4 groups. Group I (n = 6) constituted the control, group II (n = 8) was given oestradiolum benzoicum, group III (n = 8) was given progesterone, and group IV (n = 8) was given oestradiol and progesterone. Oestradiol injections resulted in a 1.5-fold increase of NA content in the ovary, a 4.5-fold increase in the tuba uterina, and a decrease of NA content in the uterine horn, cervix, and in the vagina, to 0.6 of the control NA level. Progesterone injections did not cause changes in NA content in the ovary, while there was 8.5-fold increase of NA in the oviduct, a 4-fold increase in the uterile horn, a 6-fold increase in the cervix, and a 3-fold increase in the vagina compared to the control. Joint injections of oestradiol and progesterone resulted in a decrease of NA content in the ovary to about 0.5 of the control level, and in an increase of NA content of about 5-fold in the tuba uterina, 7-fold in the uterine horn, 8-fold in the cervix, and 2-fold in the vagina. The increase of NA content in the organs was coupled with a slight increase in the density of the adrenergic innervation and the intensity of fluorescence of these nerves compared to the control. The results were compared to the results of similar but not identical studies, carried out on other mammals. 相似文献
2.
The effect of cocaine (10 μM) on the kinetics of contractile response to noradrenaline (NA) was studied in the rat epididymal
and prostatic vas deferens. Cocaine caused an acute increase in vas deferens adrenergic sensitivity primarily due to blockage
of NA neuronal capture. The presynaptic action prevailed in the epididymal half: the EC 50 value decreased 32-fold with a slight increase of the maximum adrenergic response more evident in the prostatic half.
In the presence of cocaine, the prostatic contraction to NA was mediated not by a single pool of α1-adrenoceptors like in epididymal vas deferens but by two. Its high affinity pool had the same affinity as α1-adrenoceptors of the epididymal half, the affinity value of the low one was 36-fold less, and the total maximal response
of both pools increased 4.5-fold. The differences in cocaine effect on the rat epididymal and prostatic vas deferens contractions
to NA appear to be caused by the different sources of Ca2+ involved in these responses. 相似文献
3.
Dolan BP Knowlton JJ David A Bennink JR Yewdell JW 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(11):6728-6733
Following viral infection, cells rapidly present peptides from newly synthesized viral proteins on MHC class I molecules, likely from rapidly degraded forms of nascent proteins. The nature of these defective ribosomal products (DRiPs) remains largely undefined. Using inhibitors of RNA polymerase II that block influenza A virus neuraminidase (NA) mRNA export from the nucleus and inhibit cytoplasmic NA translation, we demonstrate a surprising disconnect between levels of NA translation and generation of SIINFEKL peptide genetically inserted into the NA stalk. A 33-fold reduction in NA expression is accompanied by only a 5-fold reduction in K(b)-SIINFEKL complex cell-surface expression, resulting in a net 6-fold increase in the overall efficiency of Ag presentation. Although the proteasome inhibitor MG132 completely blocked K(b)-SIINFEKL complex generation, we were unable to biochemically detect a MG132-dependent cohort of NA DRiPs relevant for Ag processing, suggesting that a minute population of DRiPs is a highly efficient source of antigenic peptides. These data support the idea that Ag processing uses compartmentalized translation, perhaps even in the nucleus itself, to increase the efficiency of the generation of class I peptide ligands. 相似文献
4.
Buxton RC Edwards B Juo RR Voyta JC Tisdale M Bethell RC 《Analytical biochemistry》2000,280(2):291-300
Determination of the sensitivity of influenza viruses to neuraminidase (NA) inhibitors is presently based on assays of NA function because, unlike available cell culture methods, the results of such assays are predictive of susceptibility in vivo. At present the most widely used substrate in assays of NA function is the fluorogenic reagent 2'-O-(4-methylumbelliferyl)-N-acetylneuraminic acid (MUN). A rapid assay with improved sensitivity is required because a proportion of clinical isolates has insufficient NA to be detectable in the current fluorogenic assay, and because some mutations associated with resistance to NA inhibitors reduce the activity of the enzyme. A chemiluminescence-based assay of NA activity has been developed that uses a 1,2-dioxetane derivative of sialic acid (NA-STAR) as the substrate. When compared with the fluorogenic assay, use of the NA-STAR substrate results in a 67-fold reduction in the limit of detection of the NA assay, from 200 pM (11 fmol) NA to 3 pM (0.16 fmol) NA. A panel of isolates from phase 2 clinical studies of zanamivir, which were undetectable in the fluorogenic assay, was tested for activity using the NA-STAR substrate. Of these 12 isolates with undetectable NA activity, 10 (83%) were found to have detectable NA activity using the NA-STAR substrate. A comparison of sensitivity to zanamivir of a panel of influenza A and B viruses using the two NA assay methods has been performed. IC(50) values for zanamivir using the NA-STAR were in the range 1.0-7.5 nM and those for the fluorogenic assay in the range 1. 0-5.7 nM (n = 6). The NA-STAR assay is a highly sensitive, rapid assay of influenza virus NA activity that is applicable to monitoring the susceptibility of influenza virus clinical isolates to NA inhibitors. 相似文献
5.
Brouillette WJ Bajpai SN Ali SM Velu SE Atigadda VR Lommer BS Finley JB Luo M Air GM 《Bioorganic & medicinal chemistry》2003,11(13):2739-2749
We recently reported the first benzoic acid, 1-[4-carboxy-2-(3-pentylamino)phenyl]-5,5-bis(hydroxymethyl)pyrrolidin-2-one (8), that is a potent inhibitor of avian influenza A neuraminidase (N9) and, unlike other reported potent neuraminidase inhibitors, does not contain a basic aliphatic amine or guanidine nor a simple N-acetyl grouping. However, 8 was a poor inhibitor of influenza B neuraminidase. In the present study we further evaluated 8 as an inhibitor of human influenza A NA isolates, and it was effective against N2NA but found to be 160-fold less active against N1NA. We also synthesized analogues of 8 involving moderate modifications of essential substituents on the pyrrolidinone ring. Specifically, the aminomethyl (9), hydroxyethyl (10), and aminoethyl (11) analogues were prepared. Only the most conservative change (compound 9) resulted in continued effective inhibition of influenza A, in addition to a noteworthy increase in the activity of 9 for N1NA. The effectiveness of 9 against influenza B neuraminidase was furthermore improved 10-fold relative to 8, but this activity remained 50-fold poorer than for type A NA. 相似文献
6.
O S Medvedev A I Kuz'min G Ia Khulup O B Anosova 《Biulleten' eksperimental'no? biologii i meditsiny》1988,105(2):143-145
Blood pressure (BP), heart rate (HR), adrenaline (A) and noradrenaline (NA) effects of 2-desoxyglucose (500 mg/kg i.v.) were studied in conscious chronically instrumented wistar rats. A and NA contents in the blood were estimated by HPLC with electrochemical detection. In 15-40 minutes after 2-DG administration it was 13-16-fold increase in A content, 1.7-1.9-fold increase in NA content. At the same time BP fell by 5 mm Hg and HR fell by 100 beats/min. Atropine blocked bradycardia but had no effect on BP. It is concluded that high levels of endogenous A during stress are not responsible for cardiovascular responses usually observed. 相似文献
7.
Changes in plasma oxidative state with age and their influence on contractions elicited by noradrenaline in the rat tail artery. 总被引:3,自引:0,他引:3
M A Rodríguez-Martínez E C García-Cohen A Briones A B Baena E Marín M Salaices J Marín 《Life sciences》1999,65(9):915-924
The present study analyzes the changes in plasma oxidative state with age and their influence on the contractions induced by noradrenaline (NA) in endothelium-denuded segments from the tail artery of 6- (young), 24- (old) and 30- (very old) month-old Sprague Dawley rats. The sensitivity (-log EC50) to NA increased with age, this increase being higher in old than in very old animals. Moreover, the maximum response (Emax) to NA did not change in old rats, whereas decreased in very old animals. We also found a progressive increase in the plasma oxidative state with age, measured as malondialdehyde (MDA) levels, that was accompanied by a decrease in the plasma antioxidative state, measured as glutathione peroxidase activity. In addition, MDA (0.5, 1 and 10 microM) potentiated the NA responses in 6-, 24- and 30-month-old rats, respectively, without affecting Emax. In young animals, catalase (1000 U/ml) or dimethylsulfoxide (7 mM), scavengers of hydrogen peroxide or hydroxyl radicals, respectively, did not modify either the contractions induced by NA in control situation or the potentiation of these responses caused by MDA. However, the superoxide anion scavenger, superoxide dismutase (SOD, 150 U/ml), completely reversed the increase in sensitivity to NA caused by MDA, without affecting NA responses in control situation. These results suggest that the increase in NA sensitivity with age could be due, at least in part, to the enhancement of plasma oxidative state during aging. In addition, in this alteration of the responses to NA caused by MDA, the generation of superoxide anions appears to be involved. This study supports the hypothesis that the enhancement of plasma oxidative state could play an important role in the increase of vascular resistance with age. 相似文献
8.
Single injections of noradrenaline (NA) into the hypothalamic paraventricular nucleus (PVN) initiate short bouts of eating in the rat. The effect of the injections of NA (40 nM) into the PVN on gnawing was studied in satiated male rats that had displayed a reliable eating response to NA. The NA injections produced numerous bouts of prolonged and vigorous gnawing of wood pieces shaped like food pellets. The gnawing response started 0.5-2 min after the injection of NA and lasted for 20-25 min. The results suggest that the increase in gnawing and eating evoked by NA might be related to facilitation of the oral responses, and a changed sensitivity to the food related stimuli, in addition to an intrinsic increase in appetite. 相似文献
9.
E A Iumatov E A Kiiatkin 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》1983,33(6):1128-1134
Chemical sensitivity of the neurones of the medial thalamus (MT) and ventromedial hypothalamus (VMH) to noradrenaline (NA) was studied microionophoretically in conditions of 30-hour immobilization of rats. Chemical sensitivity of single neurons of MT as well as VMH during immobilization is characterized by a certain instability, showed in changes of their reactions at repeated NA applications. These changes were observed significantly more frequently in MT neurones especially at the initial stage of immobilization. At the final stage as well as in unrestrained control animals, changes of the sensitivity were seen significantly more seldom. At the initial stage of rats' immobilization a significant increase of the number of MT and VMH cells responding to NA application by the excitative type of reactions was also observed. 相似文献
10.
Leucine metabolism was measured isotopically in immature female pigs to assess the effect of acute infusions of nicotinic acid (NA) on leucine kinetics in both the fed and fasting states. After an overnight fast, immature pigs were infused with 3H-alpha-ketoisocaproate (KIC) and 14C-leucine. After a 2-hour equilibration period, an infusion of either saline or 0.4 mg/kg.min of NA was begun. NA caused a decrease in plasma glucose and an increase in plasma glucagon. During the fasting period, NA increased KIC oxidation 2-fold over controls. After feeding, plasma free fatty acids (FFA) in both groups were equivalent, but KIC oxidation was still approximately 80% higher in NA-infused animals. In addition, NA stimulated proteolysis and inhibited protein synthesis during the meal. Because plasma FFA concentrations were equal during the fed period, it is unlikely that changes in FFA concentrations are responsible for the changes in leucine metabolism observal during NA infusion. 相似文献
11.
Studies from our laboratory have demonstrated that adrenalin can restore the function of drug-induced refractory platelets to the action of physiological agonists via a novel mechanism (membrane modulation). In various disease states and clinical conditions the circulating levels of noradrenalin (NA) increase several fold more than adrenalin. Therefore, in this study the influence of NA on three well characterized platelet refractory models has been evaluated. Aspirin-exposed platelets were obtained for these studies from blood of donors who had taken one baby aspirin (80 mgs) per day for four consecutive days. Prostaglandin-exposed platelets were obtained by disaggregating ADP-induced aggregates through addition of prostaglandin E1 (1 microM). Finally, low calcium platelets were obtained by buffering cytosolic free calcium with a calcium specific cell permeant fluorophore, Quin-2 AM (60 microM). Drug-exposed platelets did not aggregate irreversibly when stirred with arachidonate (0.45 mM) or NA 5 microM). However, when treated with NA first, drug-treated platelets regained their sensitivity to the action of arachidonate and aggregated irreversibly. The ability of NA to restore the sensitivity of drug-induced refractory platelets was effectively blocked by yohimbine (10 microM), an alpha 2 adrenoceptor antagonist. Results of these studies suggest that NA, similar to the action of adrenalin, can activate membrane modulation and restore the sensitivity of platelets to the action of physiological agonists under a variety of experimental conditions. 相似文献
12.
Bio-available zinc in rice seeds is increased by activation tagging of nicotianamine synthase 总被引:1,自引:0,他引:1
Lee S Persson DP Hansen TH Husted S Schjoerring JK Kim YS Jeon US Kim YK Kakei Y Masuda H Nishizawa NK An G 《Plant biotechnology journal》2011,9(8):865-873
We generated rice lines with increased content of nicotianamine (NA), a key ligand for metal transport and homeostasis. This was accomplished by activation tagging of rice nicotianamine synthase 2 (OsNAS2). Enhanced expression of the gene resulted in elevated NA levels, greater Zn accumulations and improved plant tolerance to a Zn deficiency. Expression of Zn-uptake genes and those for the biosynthesis of phytosiderophores (PS) were increased in transgenic plants. This suggests that the higher amount of NA led to greater exudation of PS from the roots, as well as stimulated Zn uptake, translocation and seed-loading. In the endosperm, the OsNAS2 activation-tagged line contained up to 20-fold more NA and 2.7-fold more zinc. Liquid chromatography combined with inductively coupled plasma mass spectrometry revealed that the total content of zinc complexed with NA and 2'-deoxymugineic acid was increased 16-fold. Mice fed with OsNAS2-D1 seeds recovered more rapidly from a zinc deficiency than did control mice receiving WT seeds. These results demonstrate that the level of bio-available zinc in rice grains can be enhanced significantly by activation tagging of OsNAS2. 相似文献
13.
IL-6 induces lipolysis when administered to humans. Consequently, it has been hypothesized that IL-6 is released from skeletal muscle during exercise to act in a "hormonelike" manner and increase lipolysis from adipose tissue to supply the muscle with substrate. In the present study, we hypothesized that suppressing lipolysis, and subsequent free fatty acid (FFA) availability, would result in a compensatory elevation in IL-6 at rest and during exercise. First, we had five healthy men ingest nicotinic acid (NA) at 30-min intervals for 120 min at rest [10 mg/kg body mass (initial dose), 5 mg/kg body mass (subsequent doses)]. Plasma was collected and analyzed for FFA and IL-6. After 120 min, plasma FFA concentration was attenuated (0 min: 0.26 +/- 0.05 mmol/l; 120 min: 0.09 +/- 0.02 mmol/l; P < 0.01), whereas plasma IL-6 was concomitantly increased approximately eightfold (0 min: 0.75 +/- 0.18 pg/ml; 120 min: 6.05 +/- 0.89 pg/ml; P < 0.001). To assess the effect of lipolytic suppression on the exercise-induced IL-6 response, seven active, but not specifically trained, men performed two experimental exercise trials with (NA) or without [control (Con)] NA ingestion 60 min before (10 mg/kg body mass) and throughout (5 mg/kg body mass every 30 min) exercise. Blood samples were obtained before ingestion, 60 min after ingestion, and throughout 180 min of cycling exercise at 62 +/- 5% of maximal oxygen consumption. IL-6 gene expression, in muscle and adipose tissue sampled at 0, 90, and 180 min, was determined by using semiquantitative real-time PCR. IL-6 mRNA increased in Con (rest vs. 180 min; P < 0.01) approximately 13-fold in muscle and approximately 42-fold in fat with exercise. NA increased (rest vs. 180 min; P < 0.01) IL-6 mRNA 34-fold in muscle, but the treatment effect was not statistically significant (Con vs. NA, P = 0.1), and 235-fold in fat (Con vs. NA, P < 0.01). Consistent with the study at rest, NA completely suppressed plasma FFA (180 min: Con, 1.42 +/- 0.07 mmol/l; NA, 0.10 +/- 0.01 mmol/l; P < 0.001) and increased plasma IL-6 (180 min: Con, 9.81 +/- 0.98 pg/ml; NA, 19.23 +/- 2.50 pg/ml; P < 0.05) during exercise. In conclusion, these data demonstrate that circulating IL-6 is markedly elevated at rest and during prolonged moderate-intensity exercise when lipolysis is suppressed. 相似文献
14.
Noradrenaline (NA) sensitizes rat brain (Na+ + K+)-ATPase to inhibition by ethanol (EtOH). This effect of NA increases with the degree of enrichment of the enzyme: 0.1 mM NA + 0.05 M EtOH produced 27% inhibition in whole brain homogenates, 40% in 2.5-fold purified P2 fractions, and 45% in 5-fold purified microsomal fractions. The sensitization by NA was prevented by 0.1 microM phentolamine but not by 100 microM propranolol. Adrenaline and phenylephrine also sensitized the enzyme to EtOH inhibition in all of the fractions but isoproterenol did not. For all three alpha agonists the degree of sensitization was concentration dependent and the degree of reversal of this effect varied with the concentration of phentolamine added. These findings suggest that the NA + EtOH interaction is a direct effect on the membrane, probably mediated by an alpha receptor modified perturbation of the membrane microenvironment of the enzyme. 相似文献
15.
De Mello WC 《Molecular and cellular biochemistry》2007,295(1-2):53-58
The objective was to describe the changes in catecholamine levels, noradrenaline (NA) release and the ultrastructural and
immunohistochemical changes in the sympathetic nerves in the penis of STZ-diabetic rats. Amines were measured using HPLC.
Nerves were studied using immunocytochemistry for tyrosine hydroxylase, and electron microscopy. Diabetic animals were compared
with age-matched controls.
The concentration of penile NA increases at least 2.5-fold after about 10 weeks of hyperglycaemia, is maintained for over
40 weeks. The rate of release of NA in the diabetics also increases approximately by fourfold. Immunohistochemical staining
for tyrosine hydroxylase showed either no change or an increase in the levels of the enzyme around the central arteries and
the outer coverings of the corpus cavernosum. Cavernosal nerves show increased intensity of staining for tyrosine hydroxylase,
and the presence of dilated nerve fibres and engorged endings. The axons of the dorsal nerve of the diabetic penis have a
smaller cross-sectional area that is most marked in unmyelinated axons.
In the diabetic penis, the nerve endings appear to contain significantly more NA than the controls, and the turnover of noradrenaline
is increased substantially. There is immunocytochemical evidence of an increase in staining for tyrosine hydroxylase, suggesting
an increase in synthetic activity. These results are discussed in relation to the existing literature on the role of amines
in normal and disordered erectile function. In particular, the increased concentration and turnover of NA in the diabetic
rat contrasts with the fall in NA in cavernosal blood described during normal erection in humans.
This work is supported by grants from FMHS, and the Sheikh Hamdan Awards for Medical Research. 相似文献
16.
Involvement of Dopamine Neurons in the Regulation of β-Adrenergic Receptor Sensitivity in Rat Prefrontal Cortex 总被引:1,自引:1,他引:0
Denis Hervé Fabrice Trovero Gérard Blanc Paul Vezina Jacques Glowinski Jean-Pol Tassin 《Journal of neurochemistry》1990,54(6):1864-1869
The contribution of dopamine (DA) afferents to the regulation of beta-adrenergic receptor sensitivity (isoproterenol-stimulated adenylate cyclase activity) in the rat prefrontal cortex was investigated by comparing the effects of lesions affecting either both DA and noradrenaline (NA) or NA fibers alone. Bilateral 6-hydroxydopamine (6-OHDA) lesions made in the ventral tegmental area destroyed ascending DA and to a variable extent ascending NA fibers innervating the prefrontal cortex. Two opposite effects were observed depending on the extent of cortical NA denervation: (a) When NA denervation was complete (less than 4% of controls), a marked increase in the isoproterenol-sensitive adenylate cyclase activity (+78%) was found. The amplitude of this denervation supersensitivity was similar to that occurring following complete and selective destruction of NA innervation induced by bilateral 6-OHDA injections made into the pedunculus cerebellaris superior. (b) When 6-OHDA injections into the ventral tegmental area led to a partial destruction of cortical NA afferents (10-40% of control values), a hyposensitivity of the isoproterenol-induced adenylate cyclase activity (-30%) was observed. This effect contrasted with the moderate supersensitivity seen in rats with partial, but selective, destruction of NA innervation (pedunculus cerebellaris superior lesions). The hyposensitivity of beta-adrenergic receptors obtained in rats with partial lesions of cortical NA fibers, but devoid of cortical DA innervation, suggests that DA neurons may regulate, under certain conditions, the denervation supersensitivity of beta-adrenergic receptors. 相似文献
17.
M Kraakman-van der Zwet W J Overkamp A A Friedl B Klein G W Verhaegh N G Jaspers A T Midro F Eckardt-Schupp P H Lohman M Z Zdzienicka 《Mutation research》1999,434(1):17-27
Nijmegen Breakage Syndrome (NBS) is a very rare autosomal recessive chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency and a high incidence of malignancies. Cells from NBS patients are hypersensitive to ionizing radiation (IR) and display radioresistant DNA synthesis (RDS). NBS is caused by mutations in the NBS1 gene on chromosome 8q21 encoding a protein called nibrin. This protein is a component of the hMre11/hRad50 protein complex, suggesting a defect in DNA double-strand break (DSB) repair and/or cell cycle checkpoint function in NBS cells. We established SV40 transformed, immortal NBS fibroblasts, from primary cells derived from a Polish patient, carrying the common founder mutation 657del5. Immortalized NBS cells, like primary cells, are X-ray sensitive (2-fold) and display RDS following IR. They show an increased sensitivity to bleomycin (3.5-fold), etoposide (2.5-fold), camptothecin (3-fold) and mitomycin C (1.5-fold), but normal sensitivity towards UV-C. Despite the clear hypersensitivity towards DSB-inducing agents, the overall rates of DSB-rejoining in NBS cells as measured by pulsed field gel electrophoresis were found to be very similar to those of wild type cells. This indicates that the X-ray sensitivity of NBS cells is not directly caused by an overt defect in DSB repair. 相似文献
18.
Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo 总被引:2,自引:0,他引:2
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Yen HL Ilyushina NA Salomon R Hoffmann E Webster RG Govorkova EA 《Journal of virology》2007,81(22):12418-12426
Effective antiviral drugs are essential for early control of an influenza pandemic. It is therefore crucial to evaluate the possible threat posed by neuraminidase (NA) inhibitor-resistant influenza viruses with pandemic potential. Four NA mutations (E119G, H274Y, R292K, and N294S) that have been reported to confer resistance to NA inhibitors were each introduced into recombinant A/Vietnam/1203/04 (VN1203) H5N1 influenza virus. For comparison, the same mutations were introduced into recombinant A/Puerto Rico/8/34 (PR8) H1N1 influenza virus. The E119G and R292K mutations significantly compromised viral growth in vitro, but the H274Y and N294S mutations were stably maintained in VN1203 and PR8 viruses. In both backgrounds, the H274Y and N294S mutations conferred resistance to oseltamivir carboxylate (50% inhibitory concentration [IC(50)] increases, >250-fold and >20-fold, respectively), and the N294S mutation reduced susceptibility to zanamivir (IC(50) increase, >3.0-fold). Although the H274Y and N294S mutations did not compromise the replication efficiency of VN1203 or PR8 viruses in vitro, these mutations slightly reduced the lethality of PR8 virus in mice. However, the VN1203 virus carrying either the H274Y or N294S mutation exhibited lethality similar to that of the wild-type VN1203 virus. The different enzyme kinetic parameters (V(max) and K(m)) of avian-like VN1203 NA and human-like PR8 NA suggest that resistance-associated NA mutations can cause different levels of functional loss in NA glycoproteins of the same subtype. Our results suggest that NA inhibitor-resistant H5N1 variants may retain the high pathogenicity of the wild-type virus in mammalian species. Patients receiving NA inhibitors for H5N1 influenza virus infection should be closely monitored for the emergence of resistant variants. 相似文献
19.
Previously it was reported that influenza virus stimulated, nonspecific resistance was largely due to its glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The enhancement of natural killer cell activity was the intrinsic property of NA and HA. In the present study, the stimulatory effect of these glycoproteins on the murine peritoneal macrophages was studied. Electrophoretically purified glycoproteins, NA and HA, of influenza virus A/USSR/90/77 (H1N1) were administered intraperitoneally to C3H/HeN mice, with or without stearyl tyrosine (ST). Macrophages were isolated and were restimulated with phorbol myristate acetate. H2O2 secretion was determined by horseradish peroxidase dependent oxidation of phenol red assay. HA enhanced H2O2 secretion only in the presence of ST (60 nmol.mg-1.h-1), whereas NA alone stimulated H2O2 secretion (83 nmol.mg-1.h-1), by 6-fold over control (13 nmol.mg-1.h-1), and this stimulation was further increased (136 nmol.mg-1.h-1) in the presence of ST. Interleukin 1 (IL-1) activity was determined by using D10.G4.1 cells. There was a little stimulation of IL-1 activity (less than 1 U/mL) of macrophages isolated from HA-primed of HA+ST-primed mice restimulated with HA. On the other hand, IL-1 activity of macrophages isolated from NA-primed mice restimulated with NA significantly increased (102 U/mL) over control (less than 1 U/mL), and an additional 2-fold increase (231 U/mL) resulted when macrophages from NA+ST-primed mice were used. Tumor necrosis factor (TNF) activity was examined by using L929 cells. Negligible TNF activity was observed in macrophages isolated from either HA-primed or HA+ST-primed mice restimulated with HA.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
20.
Neomycin inhibits K+- and veratridine-stimulated noradrenaline release in rat brain slices and rat brain synaptosomes 总被引:2,自引:0,他引:2
The possible involvement of phosphoinositides' turnover in the process of neurotransmitter release in the central nervous system (CNS) was studied using rat brain slices and synaptosomes. A depolarizing concentration of potassium chloride (25 mM) induces an 8.6 +/- 0.4% increase of [3H]noradrenaline [( 3H]NA) fractional release in cerebral cortical slices above spontaneous release, and 15 mM KCl induces a 3-fold increase of [3H]NA release in rat brain synaptosomes. Neomycin, an aminoglycoside which binds phosphoinositides, inhibits the potassium-induced release in cortical slices with an IC50 = 0.5 +/- 0.07 mM and with IC50 = 0.2 +/- 0.03 mM in synaptosomes. Veratridine, a veratrum alkaloid which increases membrane permeability to sodium ions and causes depolarization of neuronal cells, induces a net 13.4 +/- 0.3% increase of [3H]NA fractional release above spontaneous release in cortical slices. In analogy to K+ stimulation, neomycin inhibits the veratridine-stimulated release in cortical slices with an IC50 = 0.65 +/- 0.1 mM. It appears that the recycling of phosphoinositides, which is necessary for Ca2+ mobilization, participates in the Ca2+-dependent induced neurotransmitter release in the central nervous system. 相似文献