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排序方式: 共有271条查询结果,搜索用时 93 毫秒
41.
Gurleen K. Samra Irakli Intskirveli Anitha P. Govind Christopher Liang Ronit Lazar William N. Green Raju Metherate Jogeshwar Mukherjee 《Bioorganic & medicinal chemistry letters》2018,28(3):371-377
Nicotinic acetylcholine α4β21 receptors (nAChRs) are implicated in various neurodegenerative diseases and smoking addiction. Imaging of brain high-affinity α4β21 nAChRs at the cellular and subcellular levels would greatly enhance our understanding of their functional role. Since better resolution could be achieved with fluorescent probes, using our previously developed positron emission tomography (PET) imaging agent [18F]nifrolidine, we report here design, synthesis and evaluation of two fluorescent probes, nifrodansyl and nifrofam for imaging α4β21 nAChRs. The nifrodansyl and nifrofam exhibited nanomolar affinities for the α4β21 nAChRs in [3H]cytisine-radiolabeled rat brain slices. Nifrofam labeling was observed in α4β21 nAChR-expressing HEK cells and was upregulated by nicotine exposure. Nifrofam co-labeled cell-surface α4β21 nAChRs, labeled with antibodies specific for a β2 subunit extracellular epitope indicating that nifrofam labels α4β21 nAChR high-affinity binding sites. Mouse brain slices exhibited discrete binding of nifrofam in the auditory cortex showing promise for examining cellular distribution of α4β21 nAChRs in brain regions. 相似文献
42.
Weng Naidong Wilson Shou Yu-Luan Chen Xiangyu Jiang 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,754(2):102
Use of silica stationary phase and aqueous–organic mobile phases could significantly enhance LC–MS–MS method sensitivity. The LC conditions were compatible with MS detection. Analytes with basic functional groups were eluted with acidic mobile phases and detected by MS in the positive ion mode. Analytes with acid functional groups were eluted with mobile phases at neutral pH and detected by MS in the negative ion mode. Analytes poorly retained on reversed-phase columns showed good retention on silica columns. Compared with reversed-phase LC–MS–MS, 5–8-fold sensitivity increases were observed for basic polar ionic compounds when using silica columns and aqueous–organic mobile phase. Up to a 20-fold sensitivity increase was observed for acidic polar ionic compounds. Silica columns and aqueous–organic mobile phases were used for assaying nicotine, cotinine, and albuterol in biological fluids. 相似文献
43.
Patterns of induced and constitutive monoterpene production in conifer needles in relation to insect herbivory 总被引:6,自引:0,他引:6
Studies were conducted to determine whether herbivore-induced synthesis of monoterpenes occurs in the needles of ponderosa
pine (Pinus ponderosa Lawson), lodgepole pine (P. contorta Douglas var. latifolia Engelmann), white fir (Abies concolor Lindl. and Gordon) and Engelmann spruce [Picea engelmanii (Parry) Engelm.]. In the needles of all species except Engelmann spruce, simulated herbivory significantly induced the activity
of monoterpene cyclases 4–8 days after wounding. In ponderosa pine, real herbivory by last-instar tiger moth larvae (Halisdota ingens Hy. Edwards: Lepidoptera) induced a significantly larger response (4.5-fold increase in monoterpene cyclase activity) than
did simulated herbivory (2.5-fold increase). To our knowledge, this is the first report of herbivore-induced increases in
monoterpene synthesis in needle tissue. Despite this increase in monoterpene synthesis, we observed no significant increase
in total monoterpene pool size in wounded needles compared to controls. Large increases in the rate of monoterpene volatilization
were observed in response to wounding. We conclude that the volatile losses caused by tissue damage compensate for herbivore-induced
monoterpene synthesis, resulting in no change in pool size. Tiger moth larvae consume ponderosa pine needles in a pattern
that begins at the tip and proceeds downward to midway along the needle, at which point they move to an undamaged needle.
Constitutive monoterpene concentrations and monoterpene cyclase activities were highest in the lower half of ponderosa pine
needles. The monoterpene profile also differed between the upper and lower needle halves, the lower half possessing an additional
one to four monoterpene forms. We propose that the increasing gradient in monoterpene concentrations and number of monoterpenes
along the needle from tip to base deters feeding beyond the midway point and provides time for the induction of increased
cyclase activity and production of new monoterpenes. The induction of new monoterpene synthesis may have a role in replacing
monoterpenes lost through damage-induced volatilization and preventing extreme compromise of the constitutive defense system.
Received: 4 June 1997 / Accepted: 2 December 1997 相似文献
44.
López-Hernández GY Biaggi-Labiosa NM Torres-Cintrón A Ortiz-Acevedo A Lasalde-Dominicci JA 《Cellular and molecular neurobiology》2009,29(1):41-53
Phosphorylation of the nicotinic acetylcholine receptor (nAChR) is believed to play a critical role in its nicotine-induced
desensitization and up-regulation. We examined the contribution of a consensus PKC site in the α4 M3/M4 intracellular loop
(α4S336) on the desensitization and up-regulation of α4β2 nAChRs expressed in oocytes. Position α4S336 was replaced with either
alanine to abolish potential phosphorylation at this site or with aspartic acid to mimic phosphorylation at this same site.
Mutations α4S336A and α4S336D displayed a threefold increase in the ACh-induced response and an increase in ACh EC50. Epibatidine binding revealed a three and sevenfold increase in surface expression for the α4S336A and α4S336D mutations,
respectively, relative to wild-type, therefore, both mutations enhanced expression of the α4β2 nAChR. Interestingly, the EC50’s and peak currents for nicotine activation remained unaffected in both mutants. Both mutations abolished the nicotine-induced
up-regulation that is normally observed in the wild-type. The present data suggest that adding or removing a negative charge
at this phosphorylation site cannot be explained by a simple straightforward on-and-off mechanism; rather a more complex mechanism(s)
may govern the functional expression of the α4β2 nAChR. Along the same line, our data support the idea that phosphorylation
at multiple consensus sites in the α4 subunit could play a remarkable role on the regulation of the functional expression
of the α4β2 nAChR. 相似文献
45.
Visinin-like protein (VILIP-1) belongs to the neuronal Ca2+ sensor family of EF-hand Ca2+-binding proteins that regulate a variety of Ca2+-dependent signal transduction processes in neurons. It is an interaction partner of α4β2 nicotinic acetylcholine receptor
(nAChR) and increases surface expression level and agonist sensitivity of the receptor in oocytes. Nicotine stimulation of
nicotinic receptors has been reported to lead to an increase in intracellular Ca2+ concentration by Ca2+-permeable nAChRs, which in turn might lead to activation of VILIP-1, by a mechanism described as the Ca2+-myristoyl switch. It has been postulated that this will lead to co-localization of the proteins at cell membranes, where
VILIP-1 can influence functional activity of α4-containing nAChRs.
In order to test this hypothesis we have investigated whether a nicotine-induced and reversible Ca2+-myristoyl switch of VILIP-1 exists in primary hippocampal neurons and whether pharmacological agents, such as antagonist
specific for distinct nAChRs, can interfere with the Ca2+-dependent membrane localization of VILIP-1.
Here we report, that only α7- but not α4-containing nAChRs are able to elicit a Ca2+-dependent and reversible membrane-translocation of VILIP-1 in interneurons as revealed by employing the specific receptor
antagonists dihydro-beta-erythroidine and methylallylaconitine.
The nAChRs are associated with processes of synaptic plasticity in hippocampal neurons and they have been implicated in the
pathology of CNS disorders, including Alzheimer’s disease and schizophrenia. VILIP-1 might provide a novel functional crosstalk
between α4- and α7-containing nAChRs. 相似文献
46.
Nisianakis P Giannenas I Gavriil A Kontopidis G Kyriazakis I 《Biological trace element research》2009,128(1):62-71
The effect of two different doses of selenium [1 and 50 μg selenium/100 g body weight (wt)] on nicotine-induced oxidative
damage in liver was investigated in experimental rats. Male albino rats were maintained for 60 days as follows: (1) control
group (normal diet), (2) nicotine group (0.6 mg/kg body wt)/day, (3) high-dose selenium (50 μg/100 g body wt)/day, (4) high-dose
selenium (50 μg/100 g body wt) + nicotine (0.6 mg/kg body wt)/day, (5) low-dose selenium (1 μg/100 g body wt)/day, and (6)
low-dose selenium (1 μg/100 g body wt) + nicotine (0.6 mg/kg body wt)/day. Nicotine administration caused a decrease in the
activity of antioxidant enzymes, an increase in the concentration of lipid peroxidation products and protein carbonyls and
an increase in the activity of nitric oxide synthase compared to the control group. Coadministration of nicotine and selenium
reduced the concentration of lipid peroxidation products and increased the activity of antioxidant enzymes compared to the
nicotine group. Selenium also enhanced the metabolism of nicotine. The antioxidant effect was more significant in the group
administered a low dose of selenium. 相似文献
47.
The activation of cholinergic pathways by nicotine elicits various physiological and pharmacological effects in mammals. For example, the stimulation of nicotinic acetylcholine receptors (nAChRs) leads to an antinociceptive effect. However, it remains to be elucidated which subtypes of nAChR are involved in the antinociceptive effect of nicotine on nerve injury-induced allodynia and the underlying cascades of the nAChR-mediated antiallodynic effect. In this study, we attempted to characterize the actions of nicotine at the spinal level against mechanical allodynia in an animal model of neuropathic pain, tibial nerve transection (TNT) in rats. It was found that the intrathecal injection of nicotine, RJR-2403, a selective alpha4beta2 nAChR agonist, and choline, a selective alpha7 nAChR agonist, produced an antinociceptive effect on the TNT-induced allodynia. The actions of nicotine were almost completely suppressed by pretreatment with mecamylamine, a non-selective nicotinic antagonist, or dihydro-beta-erythroidine, a selective alpha4beta2 nAChR antagonist, and partially reversed by pretreatment with methyllycaconitine, a selective alpha7 nAChR antagonist. Furthermore, pretreatment with strychnine, a glycine receptor antagonist, blocked the antinociception induced by nicotine, RJR-2403, and choline. On the other hand, the GABAA antagonist bicuculline did not reverse the antiallodynic effect of nicotine. Together, these results indicate that the alpha4beta2 and alpha7 nAChR system, by enhancing the activities of glycinergic neurons at the spinal level, exerts a suppressive effect on the nociceptive transduction in neuropathic pain. 相似文献
48.
Nicotine has been found to produce dose-dependent increases in impulsive choice (preference for smaller, sooner reinforcers relative to larger, later reinforcers) in rats. Such increases could be produced by either of two behavioral mechanisms: (1) an increase in delay discounting (i.e., exacerbating the impact of differences in reinforcer delays) which would increase the value of a sooner reinforcer relative to a later one, or (2) a decrease in magnitude sensitivity (i.e., diminishing the impact of differences in reinforcer magnitudes) which would increase the value of a smaller reinforcer relative to a larger one. To isolate which of these two behavioral mechanisms was likely responsible for nicotine's effect on impulsive choice, we manipulated reinforcer delay and magnitude using a concurrent, variable interval (VI 30 s, VI 30 s) schedule of reinforcement with 2 groups of Long-Evans rats (n = 6 per group). For one group, choices were made between a 1-s delay and a 9-s delay to 2 food pellets. For a second group, choices were made between 1 pellet and 3 pellets. Nicotine (vehicle, 0.03, 0.1, 0.3, 0.56 and 0.74 mg/kg) produced dose-dependent decreases in preference for large versus small magnitude reinforcers and had no consistent effect on preference for short versus long delays. This suggests that nicotine decreases sensitivity to reinforcer magnitude. 相似文献
49.
Franck Ceppa Younes El Jahiri Herv Mayaudon Olivier Dupuy Pascal Burnat 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2000,746(2)
A simple procedure for the determination of cotinine, major metabolite of nicotine in urine, is described. The assay involved a liquid–liquid extraction with dichloromethane in alkaline environment. The extract was dried at ambient temperature under a gentle stream of nitrogen. The residue was dissolved in 300 μl of mobile phase and 30 μl aliquot was injected via an automatic sampler into the liquid chromatograph and eluted with the mobile phase (10–9%, v/v methanol and acetonitrile, respectively in potassium dihydrogenphosphate buffer adjusted to pH 3.4) at a flow rate of 1 ml/min on a C8 Symmetry cartridge column (5 μm, 150 mm×3.9 mm, Waters) at 25°C. The eluate was detected at 260 nm. Internal standard was 2-phenylimidazole. Sensitive and specific, this technique was performed to test urine of diabetic patients (smokers and non-smokers) admitted in an endocrinology service. Urinary cotinine seems to be a better marker of smoking status than thiocyanates. 相似文献
50.
Christian Dittrich 《Proteomics》2013,13(9):1379-1380
While the genome represents a static moiety, the proteome is more dynamic and can change in response to stimuli. As such, proteomics may reveal the effect of various drugs on cellular mechanisms. Protein alterations upon exogenous perturbations are vital in outlining species‐to‐species differences that cannot otherwise be measured quantitatively. Specifically, nicotine has been shown to be an independent risk factor for a multitude of diseases. In pancreatic research its mechanism of action remains unresolved. The pioneering work of Paulo et al. (Proteomics 2013, 13, 1499–1512) is a major step toward understanding the role of nicotine, a principal toxin in cigarette smoke, in pancreatic disease. Equally important, Paulo et al. examine the effect of nicotine on stellate cells across three species, demonstrating the importance of identifying species‐specific effects in translational research. 相似文献