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| 1 | K-ATP channel openers facilitate glutamate uptake by GluTs in rat primary cultured Astrocytes显示文摘Increasing evidence, including from our laboratory, has revealed that opening of ATP sensitive potassium channels(K-ATP channels) plays the neuronal protective roles both in vivo and in vitro. Thus K-ATP channel openers(KCOs) have been proposed as potential neuroprotectants. Our previous studies demonstrated that K-ATP channels could regulate glutamate uptake activity in PC12 cells as well as in synaptosomes of rats. Since glutamate transporters(GluTs) of astrocytes play crucial roles in glutamate uptake and KATP channels are also expressed in astrocytes, the present study showed whether and how KATP channels regulated the function of GluTs in primary cultured astrocytes. The results showed that nonselective KCO pinacidil, selective mitochondrial KCO diazoxide, novel, and blood-brain barrier permeable KCO iptakalim could enhance glutamate uptake, except for the sarcolemmal KCO P1075. Moreover pinacidil, diazoxide, and iptakalim reversed the inhibition of glutamate uptake induced by 1-methyl-4-phenylpyridinium(MPP+). These potentiated effects were completely abolished by mitochondrial K-ATP blocker 5-hydroxydecanoate. Furthermore, either diazoxide or iptakalim could inhibit MPP+-induced elevation of reactive oxygen species (ROS) and phosphorylation of protein kinases C(PKC). These findings are the first to demonstrate that activation of K-ATP channel, especially mitochondrial K-ATP channel, improves the function of GluTs in astrocytes due to reducing ROS production and downregulating PKC phosphorylation. Therefore, the present study not only reveals a novel pharmacological profile of KCOs as regulators of GluTs, but also provides a new strategy for neuroprotection. | Sun, X. L. Zeng, X. N. Zhou, F. Dai, C. P. Ding, J. H. Hu, G. Nanjing Med Univ,Dept Anat Histol & Pharmacol,Neuropharmacol Lab,Nanjing 210029,Jiangsu,Peoples R China. | 2008 | 南京医科大学学报(自然科学版)2008，28，6： | 7 |
| 2 | Pathological and biochemical alterations of astrocytes in ovariectomized rats injected with D-galactose:A potential contribution to Alzheimer's disease processes显示文摘Astrocytes are implicated in the pathological changes of Alzheimer's disease. Our previous studies have demonstrated that estrogen deprivation and oxidative stress act synergistically to accelerate the progress of Alzheimer's disease. Long-term D-galactose injection combined with ovariectomy may serve as a rodent model for Alzheimer's disease. To address the potential contribution of astroglia to the Alzheimer's disease pathogenesis, we investigated pathological and biochemical alterations of astrocytes under this animal model. Ovadectomized rats injected with D-galactose for 2 weeks showed extensive localization of glial fibrillary acidic protein immunoreactive astrocytes and slightly elevated glutathione levels in the hippocampus without significant impairments in the water maze test and deficits of the cholinergic analyses, compared to the saline-injected rats. Ovariectomized rats injected with D-galactose for 6 weeks, however, exhibited degeneration of astrocytes and decreased glutathione levels in the hippocampus, accompanied with severe dysfunction of behavioral test and deficiency of cholinergic terminals. Electron microscopy further confirmed the pathological changes of astrocytes, especially in the aggregated area of synapse and brain microvessels. Consistent with degeneration of perivascular astrocytic endfeet, analysis of the horseradish peroxidase demonstrated an impairment of the blood-brain barrier permeability. These findings indicate that biochemical and pathological alterations of astrocytes may partially contribute to exacerbating neuronal deficits in the course of Alzheimer's disease. Restoring neuroprotective potential of astrocytes may be a useful therapeutic target for Alzheimer's disease and other neurodegenerative diseases. | Hua, X. D. Lei, M. Ding, H. Han, Q. Y. Hu, G. Xiao, M. Nanjing Med Univ,Dept Anat Histol & Pharmacol,Jiangsu Prov Key Lab Neurodegenerat,Nanjing 210029,Peoples R China. | 2008 | 南京医科大学学报(自然科学版)2008，28，6： | 4 |
| 3 | Hypoxia-reoxygenation- in cultured neonatal rat cardiomyocyets effect of prostaglandin E 显示文摘 | MaXQ FuRF induced apoptosis and the protective Pharmacol Physiol Feng G Q | 2005 | Clin Exp2005，32，12： | 1 |
| 4 | Anti-inflammatory effect of atorvastatin in patients with aortic sclerosis or mild aortic stenosis inde- pendent of hypercholesterolemia 显示文摘 | Pharmacol Rep | 2010 | Cardiovasc Drugs Ther2010，62，6： | 1 |
| 5 | Effect of Pongamia pinnata flowers on blood glucose and oxidative stress in alloxan induced diabetic rats显示文摘 | PHARMACOL J | 2006 | Indian Res Lett2006，38，1： | 1 |
| 6 | Free androgen index and Irisin in polycystic ovary syndrome显示文摘 | irisin levels in Med Pharmacol Li H Xu X Wang X | 2016 | J Endocrinol Invest2016，39，5： | 1 |
| 7 | Treatment of severe familial cholesterolemia in childhood with sitosterol and sitostanol显示文摘 | PHARMACOL BECKER M STAAB D | 1993 | Pediatr1993，122，： | 1 |
| 8 | Neuronal ion channels as the target sites of insecticides显示文摘 | NARAHASHI T PHARMACOL | 1976 | Pharmacol Toxicol1976，78，： | 1 |
| 9 | A retinoic acid receptor beta / gamma-selective prodrug (tazarotene) plus a retinoid Xreceptor ligand induces extracellular signal-regulated kiactivation, retinoblastoma hypophosphorylation, Goarrest, and cell differentiation 显示文摘 | Yen A fenning R Chandraratna R Mol Pharmacol | 2004 | Mol Pharmacol2004，66，6： | 1 |
| 10 | Candesart an and sympat hetic heart failure 显示文摘 | Hikosaka M Yuasa F Yuyama R and arterial barore-flexsen sitivity nerve activity inpatients with mild Cardiovasc Pharmacol 2002 40(6) | 2002 | J2002，，： | 1 |
| 11 | Comparison of the effects of unfractionated heparin and the low-molecular-weight heparins dalteparin and enoxaparin on spontaneous platelet aggregation and adenosine diphosphate activity in platelets during the third trimester of pregnancy显示文摘 | AJAYI A A PHARMACOLS F B COOPER J | 2007 | Methods Find Exp Clin Pharmacol2007，29，： | 1 |
| 12 | Molecular evolution of the fibulins: implications on the functionality of the elastic fibulins 显示文摘 | Pharmacol Segade F | 2010 | Gene2010，464，12： | 1 |
| 13 | and antioxidant status in acute insecticide poisoning 显示文摘 | VIDYASAGAR J Oxidative stress organophosphoreus Pharmacol 2004 KARUNAKAR N REDDY M S | 2004 | Indian J2004，36，2： | 1 |
| 14 | Molecular mechanistic explanation for the spectrum of cholestatic disease caused by the $320F variant of ABCtN 显示文摘 | Functional Characterization of Low Phospholipid-Associated Korean J Physiol Pharmacol Andress EJ Nicolaou M Romero MR | 2014 | Hepatology2014，59，5： | 1 |
| 15 | blieroRNA-144 suppresses tumorigene- sis and tumor progression of astrocytoma by targeting EZH2 显示文摘 | Role of micro-RNA (miRNA) in Eur Rev Med Pharmacol Sci Lin L Zheng Y Tu Y | 2015 | Hum Pathol2015，46，7： | 1 |
| 16 | Enhanced intracellular calcium induced by urocortin is involved in degranulation of rat lung mast cells显示文摘Corticotropin-releasing factor(CRF), which activates the hypothalamic-pituitary-adrenal axis under stress, also has proinflammatory peripheral effects possibly through mast cells. The purpose of this study was to investigate the effect of urocortin (UCN), a 40-amino-acid CRF family peptide, on degranulation and intracellular calcium of rat lung mast cells. The activation and degranulation of mast cells were observed by Toluidine blue staining and transmission electron microscope. The intracellular calcium was investigated using confocal laser scanning microscopy and flow cytometry. The results indicated that all the three different concentrations of UCN(0.1, 1 and 10 mu M) significantly induced the activation and degranulation of rat lung mast cells in vitro. This effect was markedly blocked by selective CRF receptor 1(CRF-R1) antagonist antalarmin, but not by specific CRF receptor 2(CRF-R2) antagonist antisauvagine-30(anti-Svg-30). The results also showed that UCN caused a rapid peak increase inCa2+(i) at point of 300s after UCN treatment, followed by a decrease to a sustained plateau phase. The peak increase inCa2+(i) induced by UCN was significantly inhibited by antalarmin, but not by anti-Svg-30. This effect of UCN onCa2+(i) in rat lung mast cells was also found by flow cytometry. Regression analysis revealed a positive correlation between mast cells degranulation extent and the maximum value ofCa2+(i)(P < 0.01). Taken together, our present study suggested that UCN induced the increase of Ca2+(i) and degranulation of rat lung mast cells through CRF-R1. These findings may have implications for the pathophysiology of allergic and inflammatory lung disorders such as asthma, which is closely associated with mast cell activation and degranulation. Copyright (c) 2008 S. Karger AG, Basel. | Wu, Y. Q. Hu, J. Zhang, R. J. Zhou, C. H. Xu, Y. H. Guan, X. W. Li, S. S. (Nanjing Med Univ, Dept Pharmacol, Nanjing 210029, Peoples R China. Xuzhou Med Coll, Dept Pharmacol, Xuzhou, Peoples R China) | 2008 | 南京医科大学学报(自然科学版)2008，28，6： | 1 |
| 17 | The role of male sex hormones in the healing process of lingual and gastric ulcerations显示文摘 | Machowska female and preexisting Pharmacol A Szlachcic A Pawlik M | 2004 | J Physiol2004，55，2： | 1 |
| 18 | Keratocyte apoptosis after corneal surgery 显示文摘 | Pharmacol Exp Ther 2000 295:889Helena MC Baerveldt F Kim WJ | 1998 | Invest Ophthalmol Vis SCi1998，39，： | 1 |
| 19 | Intestinal absorption of digoxin and interaction with nimodipine in rats显示文摘 | Gastrointestinal absorption of Fundam Clin Pharmacol 1999 Kilic F S Batu O Sirmagul B | 2004 | Pol J Pharmacol2004，56，： | 1 |
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