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21.
Pre- and Posttranslational Regulation of β-Endorphin Biosynthesis in the CNS: Effects of Chronic Naltrexone Treatment 总被引:1,自引:1,他引:0
David M. Bronstein Nicola C. Day Howard B. Gutstein Keith A. Trujillo Huda Akil 《Journal of neurochemistry》1993,60(1):40-49
Abstract: There appear to be two anatomically distinct β-endorphin (βE) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on βE biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different βE-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total βE-ir, different molecular weight immunoreactive β-endorphin (βE-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total βE-ir concentrations by 30–40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on βE-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to ~ 140% of control values. These data suggest that arcuate POMC neurons are up-regulated after chronic NTX treatment (whereas NTS and spinal cord systems remain unaffected) and that they appear to be under tonic inhibition by endogenous opioids. Chromatographic analyses demonstrated that, after chronic NTX pelleting, the ratio of full length βE1–31 to more processed βE-ir peptides (i.e., βE1–27 and βE1–26) tended to increase in a dose-dependent manner in diencephalic areas. Because βE1–31 is the only POMC product that possesses opioid agonist properties, and βE1–27 has been posited to function as an endogenous anatgonist of βE1–31, the NTX-induced changes in the relative concentrations of βE1–31 and βE1–27/βE1–26 may represent a novel regulatory mechanism of POMC cells to alter the opioid signal in the synapse. 相似文献
22.
L. Pradier E. Heuillet J. P. Hubert M. Laville S. Le Guern A. Doble 《Journal of neurochemistry》1993,61(5):1850-1858
Abstract— In the human astrocytoma cell line U 373 MG, application of substance P (SP) leads to a transient increase in cytosolic calcium concentration and to a biphasic current response in voltage-clamped cells. Using these two functional assays we have characterized pharmacologically the SP response in U 373 MG cells. SP and [l -Pro9]SP displayed high potencies in both assays with EC50values of 2.5 ± 10?9M and 1 ± 10?9M on calcium responses and 110?9M and 510?9M on ion current responses, respectively. The high potency of SP and [l -Pro9]SP as well as the low potency of [Lys5,MeLeu9,N-Leu10]neurokinin A(4-10) and the inactivity of senktide demonstrate the NK1-type pharmacology of these responses. Furthermore, the NK1 antagonists (±)-CP 96,345, its chloro analogue, (±)-cis-3-(2-chlorobenzylamino)-2-benz-hydrylquinuclidine, and RP 67580 were potent antagonists of both SP responses. For the calcium mobilization induced by SP (1 (10?7M), the IC50 values for the three antagonists were 4 ± 10?10M, 4 ± 10?9M, and 9 ± 10?9M, respectively, whereas on the current response evoked by SP 10?8M), the IC50 values were 8 ± 10?9M, 2.4 ± 10?8M, and 1.2 10?7M, respectively. Despite differences in the absolute IC50 values obtained with both techniques, the relative potencies of the three antagonists correlate fairly well. The U 373 MG cell line provides a useful model system for studies of the pharmacology of the human NK1receptor and its transduction mechanisms at the level of second messengers and modulation of ion currents. 相似文献
23.
Rudrapatnam N. Tharanathan Akira Yokota Heike Rau Hubert Mayer 《Archives of microbiology》1993,159(5):445-452
Lipopolysaccharides (LPS), isolated from four Mycoplana species, i.e. the type strains of M. bullata, M. segnis, M. ramosa and M. dimorpha, were characterized onto their chemical composition and their respective lipid A-types. Those of M. bullata and M. segnis showed on DOC-PAGE an R-type character and had lipid A's of the Lipid ADAG-type which exclusively contained 2,3-diamino-2,3-dideoxy-d-glucose as lipid A sugar. LPS's of M. ramosa and M. dimorpha showed, although only weakly expressed, ladder-like patterns on DOC-PAGE indicating some S-type LPS's and lipid A of the d-glucosamine type (Lipid AGlcN). M. bullata LPS contained mannose and glucose in major amounts and additionally l-glycero-d-mannoheptose, whereas M. segnis LPS was composed of rhamnose, mannose and glucose together with both, d-glycero-d-manno- and l-glycero-d-manno-heptoses in a molar ratio of 1:2. All LPS's contained 2-keto-3-deoxy-octonic acid (Kdo), phosphate and an unidentified acidic component X. In addition to X, M. segnis LPS contained glucuronic and galacturonic acids, whereas M. ramosa LPS contained only galacturonic acid. Acetic acid hydrolysis of the LPS resulted in splitting off lipid A moieties, very rich in 3-hydroxy fatty acids, in particular in 3-OH-12:0 (in Lipid ADAG), or in 3-OH-14:0 (in Lipid AGlcN). Analysis of the 3-acyloxyacyl residues revealed major amounts of amide-linked 3-OH(3-OH-13:0)12:0 in lipid A of M. bullata and 3-OH(12:0)12:0 in lipid A of M. segnis. The rare 4-oxo-myristic acid (4-oxo-14:0) was observed only in M. bullata LPS, where it is ester-linked. Amide linked diesters could not be traced in M. ramosa and M. dimorpha. All four lipid A's lacked erster-bound acyloxyacyl residues.Non-standard abbreviations DAG
2,3-diamino-2,3-dideoxy-d-glucose
- Kdo
2-keto-3-deoxy-octonate
- LPS
lipopolysaccharide
- PITC
phenyl isothiocyanate
- NANA
N-acetyl neuraminic acid 相似文献
24.
Seiji Ichida Tetsuyuki Wada Satori Nakazaki Naruhisa Matsuda Hiroyuki Kishino Takafumi Akimoto 《Neurochemical research》1993,18(5):633-638
The characteristics of the specific bindings of [3H](+)PN200-110 (PN: L-type Ca channel antagonist) and [125I]-conotoxin G VI A (-CgTX: neuronal L-or N-type Ca channel antagonist) to crude membranes from undifferentiated neuroblastoma x glioma hybrid NG108-15 (NG108-15) cells and differentiated cells induced with dibutyryl cAMP (Bt2cAMP) were examined, because we have already observed that the magnitude and rate of KCL-stimulated45Ca uptake by NG108-15 cells increased progressively during differentiation of the cells induced with Bt2cAMP (unpublished results). The specific binding of [3H](+)PN to these crude membranes was saturable at various concentrations of 2.5–5.0 nM [3H](+)PN. Scatchard analysis showed that the specific binding of [3H](+)PN at equilibrium was significantly increased after differentiation of the NG108-15 cells with Bt2cAMP, but that the apparent Kd value for the specific binding of [3H](+)PN was not influenced by treatment with Bt2cAMP. The specific binding of [3H](+)PN to crude membranes from Bt2cAMP-treated NG108-15 cells was inhibited by a calcium agonist and antagonists, the order of their inhibitory potencies being (+)PN>nitrendipine>(–)PNBay K 8644diltiazem = verapamil. Thus, PNs showed significant stereoselective inhibition of the specific binding of [3H(+)PN. On the other hand, [125I]-CgTX at concentrations of 0.075–0.6 nM showed scarcely any specific binding to these crude membranes, although at 0.6 nM it showed specific binding to crude membranes from rat brain in the same experimental conditions. These results suggest that the increase in magnitude or rate of KCl-stimulated45Ca uptake during differentiation of NG108-15 cells is partially due to quantitative alteration of voltage-sensitive Ca channels in the cells, and that there are scarcely any specific binding sites for [125I]-CgTX on Bt2cAMP-treated or untreated NG108-15 cells. 相似文献
25.
Kazuhito Hisatsune Takehiro Iguchi Yuji Haishima Norihiko Tamura Seiichi Kondo 《Microbiology and immunology》1993,37(2):143-147
The chemical properties of a lipopolysaccharide (LPS) isolated from a new O-antigenic form (O13) of Vibrio parahaemolyticus were investigated. The LPS contained glucose, galactose, L -glycero-D -manno-heptose and glucosamine. 2-Keto-3-deoxy-octonate (KDO) was not detected in the LPS by the periodate-thiobarbituric acid test (Weissbach's reaction) under conventional hydrolysis conditions. Instead, phosphorylated KDO (X1 and X2) was found in its strong-acid hydrolysate. This sugar composition was identical to that of V. parahaemolyticus O3, O5 and O11 LPS, indicating that, based on the sugar composition, O13 LPS belongs to Chemotype III to which O3, O5 and O11 belong. In addition, structural study demonstrated the presence of KDO 4-phosphate in its inner-core region. 相似文献
26.
Anna Swierzko Lore Brade Elisabeth C. Höffgen Helmut Brade 《FEMS immunology and medical microbiology》1993,7(3):265-270
Abstract Rabbit polyclonal antibodies against the lipopolysaccharide (LPS) of the Rd1 P− mutant strain R7 of Salmonella minnesota were serologically characterized using R7 LPS, dephosphorylated LPS, deacylated LPS, deacylated, dephosphorylated and reduced LPS, and synthetic partial structures. The latter comprised partial structures of the core region of Rd1 P− LPS bound to the β 1 → 6-linked glucosamine disaccharide with two amide-linked 3-hydroxytetradecanoic acid residues or artificial glycoconjugates comprised of the synthetic oligosaccharides coupled to bovine serum albumin. Using a passive hemolysis and an enzyme immunoassay, absorption and inhibition experiments, the antibody specificities present could be determined. One group of antibodies required components of the core region and the phosphorylated glucosamine disaccharide of the lipid A moiety for binding. The majority of phosphate-independent antibodies was directed against the trisaccharide l -glycero-α- d -manno-heptopyranose(1 → 3)- l -glycero-α- d -manno-heptopyranose(1 → 5)3-deoxy- d -manno-octulosonic acid. Antibodies against the 1 → 3- and 1 → 7-linked heptose disaccharides and against a single heptose were also detected, however, with low titers. No antibodies were found which required the presence of fatty acids. 相似文献
27.
苄基异喹啉化合物是一类钙调素拮抗剂.对新合成的双苄基异喹啉化合物 D20对钙调素依赖的磷酸二酯酶的抑制作用进行了研究,IC50=5μmol/L,表明其拮抗作用大于三氟啦嗪,是强的拮抗剂.荧光分析表明,钙调素与化合物 D20的结合常数为2.64(μmol/L)-1,一个化合物 D20分子与两个钙调素分子结合,并显示了结合方向性及空间位阻影响. 相似文献
28.
29.
以肠炎沙门氏菌脂多糖为抗原,用酶标法测定Vi多糖菌苗免疫血清的抗LPS抗体。各Vi多糖菌苗组免疫后1月,6月的抗LPS水平均显著高于免前(P<0.0001),对照组无显著差异(p>0.1)。两30μg菌苗组抗LPS阳转率均约为15%。提纯Vi多糖菌苗所含的微量伤寒LPS,也可能为接种者提供一定的保护作用。 相似文献
30.
A wild type strain ofVerticillium lecanii and a mutant strain with increased tolerance to the fungicide benomyl were evaluated in greenhouse experiments for effects on Heterodera glycines populations. Nematodes were applied at 300 eggs and juveniles per 4,550-cm³ pot (two soybean plants in 4,990 g loamy sand per pot) and at both 300 and 10,000 eggs and juveniles per 1,720-cm³ pot (one soybean plant in 2,060 g sand per pot). With 300 nematodes added per pot, both V. lecanii strains significantly reduced nematode populations in loamy sand (fungus applied at 0.02% dry weight per dry weight loamy sand) and sand (0.006% and 0.06% fungus application rates). The mutant strain applied at 0.002% to sand also significantly reduced cyst numbers. When 10,000 nematodes were added per pot, only the mutant strain at 0.06% significantly decreased population. Various media were tested for isolation of the fungus strains from prills, loamy sand, and sand, but the fungi were recovered from few of the greenhouse pots. 相似文献