Abstract：
:For the development of efficient pulmonary delivery systems for protein and peptide drugs, it is important to understand their transport mechanisms in alveolar epithelial cells. In this study, the uptake mechanism for FITC-insulin in cultured alveolar epithelial cell line RLE-6TN was elucidated. FITC-insulin uptake by RLE-6TN cells was time-dependent, temperature-sensitive, and concentration-dependent. The uptake was inhibited by metabolic inhibitors, cytochalasin D, clathrin-mediated endocytosis inhibitors, and dynasore, an inhibitor of dynamin GTPase. On the other hand, no inhibitory effect was observed with caveolae-mediated endocytosis inhibitors and a macropinocytosis inhibitor. Intracellular FITC-insulin was found to be partly transported to the basal side of the epithelial cell monolayers. In addition, colocalization of FITC-insulin and LysoTracker Red was observed on confocal laser scanning microscopy, indicating that FITC-insulin was partly targeted to lysosomes. In accordance with these findings, SDS-PAGE/fluoroimage analysis showed that intact FITC-insulin in the cells was eliminated with time. The possible receptor involved in FITC-insulin uptake by RLE-6TN cells was examined by using siRNA. Transfection of the cells with megalin or insulin receptor siRNA successfully reduced the corresponding mRNA expression. FITC-insulin uptake decreased on the transfection with insulin receptor siRNA, but not that with megalin siRNA. These results suggest that insulin is taken up through endocytosis in RLE-6TN cells, and after the endocytosis, the intracellular insulin is partly degraded in lysosomes and partly transported to the basal side. Insulin receptor, but not megalin, may be involved at least partly in insulin endocytosis in RLE-6TN cells.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Oda K,Yumoto R,Nagai J,Katayama H,Takano Mdoi
10.1016/j.ejphar.2011.10.003subject
Has Abstractpub_date
2011-12-15 00:00:00pages
62-9issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(11)01204-0journal_volume
672pub_type
杂志文章abstract：:The effect of several pyrolysate mutagens on the benzodiazepine and GABA receptors was investigated. Of amino-gamma-carbolines, Trp-P-1 antagonized the suppressive effect of diazepam on the pentylenetetrazol-induced convulsions and death, whereas Trp-P-2 by itself precipitated seizures and death in male mice. Both Trp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90106-7
更新日期：1984-02-10 00:00:00
abstract：:delta-Aminolaevulinic acid (ALA) inhibited spontaneous contractions and contractions induced by acetylcholine, barium chloride or ouabain in rabbit duodenum preparations suspended in Ringe-Locke solution. Concentrations of ALA between 25--100 micrograms/ml reduced amplitude of spontaneous contractions and at levels ab...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90229-0
更新日期：1980-06-27 00:00:00
abstract：:The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, was evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in incremental doses of 0.3 mg/kg at 1 min intervals until a conve...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90404-1
更新日期：1978-10-01 00:00:00
abstract：:In the present study, the role of reactive oxygen species and the contribution of antioxidant defence in the time course of changes in acetylcholine-stimulated endothelium-dependent and sodium nitroprusside-stimulated endothelium-independent relaxation were investigated in aortic rings isolated from 6-month streptozot...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00140-0
更新日期：2000-03-31 00:00:00
abstract：:Multiple forms of phosphodiesterase have been reported in many tissues. Phosphodiesterase 6, a cGMP-specific phosphodiesterase, is described as a photoreceptor cell-specific phosphodiesterase. Phosphodiesterase 6 is known to play a crucial role in visual function. A novel phosphodiesterase inhibitor, GF248 (5["(propox...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00346-x
更新日期：1998-07-10 00:00:00
abstract：:beta-Carbolines (including harmane and pinoline) stimulate insulin secretion by a mechanism that may involve interaction with imidazoline I(3)-receptors but which also appears to be mediated by actions that are additional to imidazoline receptor agonism. Using the MIN6 beta-cell line, we now show that both the imidazo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.08.018
更新日期：2004-10-06 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00693-2
更新日期：2000-10-20 00:00:00
abstract：:125I-labelled endothelin-1 was used to identify specific high affinity endothelin-1 binding sites in left ventricular and brain membranes harvested from female age-matched normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Relative to results obtained for brain membranes from normotensive ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90272-8
更新日期：1990-02-27 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90112-6
更新日期：1981-12-17 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.03.002
更新日期：2019-06-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90018-x
更新日期：1986-12-02 00:00:00
abstract：:Recent data show that corticolimbic expression of the effector immediate early gene Arc is up-regulated by standard antidepressant drugs. Here, we tested the effect upon Arc expression of a novel antidepressant and selective 5-hydroxytryptamine/noradrenaline reuptake inhibitor (SNRI), (-)1-(1-dimethylaminomethyl) 5-me...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.03.002
更新日期：2004-04-12 00:00:00
abstract：:The effects of treatment with anxiogenic or anxiolytic agents and exposure to acute restraint stress on emotional behavior in mice were examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e., total locomotor activity, nu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00223-4
更新日期：1998-05-29 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90233-8
更新日期：1993-05-12 00:00:00
abstract：:Atropine-induced locomotor stimulation was investigated in the developing rat pretreated with 6-hydroxydopa at birth. The locomotor stimulation by atropine was first observed on day 20 and gradually increased with age. The treatment with 6-hydroxydopa potentiated atropine-induced locomotor stimulation on days later th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90149-8
更新日期：1978-08-15 00:00:00
abstract：:In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90273-7
更新日期：1992-01-28 00:00:00
abstract：:Genetic factors significantly contribute to the determination of human personality traits assessed by self-report questionnaires. However, only in the past few years have common genetic polymorphisms especially the dopamine D4 receptor and the serotonin transporter promoter region been associated with specific persona...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(00)00852-9
更新日期：2000-12-27 00:00:00
abstract：:The effect of Ca2+ on the oxytocin-induced, sustained contraction of rat uterine muscle in Ca-free medium after prolonged incubation with 3 mM EGTA (Ca-free contraction) was investigated. A micromolar concentration of Ca2+ caused phasic contraction followed by relaxation while a submicromolar concentration caused rela...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90286-x
更新日期：1987-08-21 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00738-5
更新日期：2001-02-09 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.02.035
更新日期：2013-04-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)94196-5
更新日期：1990-11-13 00:00:00
abstract：:In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.07.014
更新日期：2015-10-05 00:00:00
abstract：:The vasoactive properties of the neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and some selective analogues were assessed in the arterial and venous mesenteric beds of the rat. Although both sides of the mesenteric vasculature displayed endothelium-dependent relaxation in response to acetylcho...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90860-s
更新日期：1991-11-12 00:00:00
abstract：:The electrical activity of the sino-atrial node was studied after the selective cannulation of its artery in the intact open-chest dog. After tetrodotoxin infusion and despite cardiac arrest, a slow rhythmic activity was recorded from the sinus epicardial electrode. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90227-3
更新日期：1978-05-01 00:00:00
abstract：:The ability of the conotoxin rho-TIA, a 19-amino acid peptide isolated from the marine snail Conus tulipa, to antagonize contractions induced by noradrenaline through activation of alpha1A-adrenoceptors in rat vas deferens, alpha1B-adrenoceptors in rat spleen and alpha1D-adrenoceptors in rat aorta, and to inhibit the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.12.011
更新日期：2005-01-31 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：2019-09-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(93)90009-f
更新日期：1993-12-01 00:00:00
abstract：:Pentoxifylline, a methylxanthine derivative, has been widely used to improve erythrocyte deformability and capillary blood circulation in patients with claudication and cerebrovascular disorders as well as in animals with sepsis. Here, we investigate the effects of pentoxifylline on the hypotension, vascular hyporeact...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00265-4
更新日期：1999-05-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.10.004
更新日期：2013-11-15 00:00:00
abstract：:Infusion of renal side population (SP) cells, enriched with adult stem-like cells, can ameliorate acute renal failure. We investigated the effects of an angiotensin II type 1 (AT(1)) receptor antagonist, valsartan on SP cell changes in renal injury by ureteral obstruction. Renal SP fraction was reduced by 38%, and the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.07.032
更新日期：2007-11-14 00:00:00
