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：:Contractile responses to endothelin, 5-hydroxytryptamine (5-HT), noradrenaline and potassium were obtained on isolated preparations of pulmonary artery from rats made pulmonary hypertensive by an injection of monocrotaline (105 mg/kg s.c.) 4 weeks previously. When compared with data obtained in control rats, the poten...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90524-a
更新日期：1990-02-06 00:00:00
abstract：:The overactivation of glutamate receptors is a major cause of Ca(2+) overload in cells, potentially leading to cell damage and death. There is an abundance of agents and mechanisms by which glutamate receptor activation can be prevented or modulated in order to control these effects. They include the well-established,...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(02)01851-4
更新日期：2002-07-05 00:00:00
abstract：:Salvianolic acid B (SalB) is a polyphenolic compound found in Salvia miltiorrhiza Bunge that has several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether SalB has neuroprotective effects in an amyloid β (Aβ) peptide-induced Alzheimer's disease mouse model. Mice were injected ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.02.015
更新日期：2013-03-15 00:00:00
abstract：:Soluble guanylate cyclase, a heterodimer consisting of an alpha- and a heme-containing beta-subunit, is the major receptor for the biological messenger nitric oxide (NO) and is involved in various signal transduction pathways. The heme moiety of the enzyme is bound between the axial heme ligand histidine(105) and the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.02.046
更新日期：2005-04-18 00:00:00
abstract：:The glutamate receptor agonists, kainate and N-methyl-D-aspartate (NMDA) result in the elevation of intracellular calcium levels ([Ca2+]i) in primary cultures of cerebellar granule neurons. Several tricyclic antidepressants (TCAs), amitriptyline (0.5-1 microM), desipramine (1 microM) and doxepine (1 microM) partially ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90579-s
更新日期：1992-08-14 00:00:00
abstract：:Patients with spinal cord injury (SCI) undergo severe loss of bone mineral below the level of lesion, and data on available treatment options after SCI is scarce. The aim of this work was to investigate the therapeutic effect of cannabidiol (CBD), a non-psychoactive cannabis, on sublesional bone loss in a rat model of...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.05.011
更新日期：2017-08-15 00:00:00
abstract：:Glomeruli isolated from rat kidney cortex were incubated with adenosine in the presence or absence of verapamil and calcium and their change in cross-sectional area was recorded. Adenosine induced a 10% decrease in glomerular cross-sectional area. This decrease was blocked by verapamil or a calcium-free medium. The re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90371-2
更新日期：1987-02-24 00:00:00
abstract：:Inflammation has been reported to be closely related to exaggeration of cerebral ischemia and neurodegenerative diseases. Microglia, resident immune cells in the central nervous system, can be activated in response to neuronal injury and produce proinflammatory cytokines, resulting in further aggravation of neuronal i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.12.014
更新日期：2017-01-15 00:00:00
abstract：:Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, reduced in a dose-dependent fashion the ischemic contracture due to low perfusion (0.2 ml/min) of isovolumic left heart of rabbit and abolished the irregular rhythm of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 m...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90687-x
更新日期：1987-03-31 00:00:00
abstract：:Intracellular accumulation of Mn2+ augmented the contractions induced by norepinephrine and acetylcholine in the guinea pig isolated vas deferens. Contractions repeatedly induced by norepinephrine, acetylcholine, or a high concentration of K+ decreased depending on the incubation time in Ca(2+)-free medium. The rate o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00664-8
更新日期：1996-01-11 00:00:00
abstract：:Many studies have shown that anti-inflammatory agents are effective in the treatment of endometriosis. β-Caryophyllene exerted a potent anti-inflammatory effect in vivo. However, its effect on endometriosis has not been investigated. This study aims at investigating the effect of β-caryophyllene on endometriosis and o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.01.011
更新日期：2013-02-28 00:00:00
abstract：:In Krebs solution (3.36 mM Ca2+), the maximal contractile response of human ileal and urinary bladder detrusor muscle to acetylcholine (ACh) was 40-60% that to carbachol (CCh). The maximum response to ACh was reached at a bath concentration of about 1 microM and was maintained throughout a range extending to 100 micro...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90698-9
更新日期：1986-04-09 00:00:00
abstract：:The effect of estrogen on neointimal formation in injured rat arteries has been reported to be a sexual dimorphic effect. Recently, it has been reported that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exhibit vasoprotective effects, which are independent of their cholesterol-lowerin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.09.036
更新日期：2006-12-28 00:00:00
abstract：:The potency of the serotonin 1A (5-HT1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), to induce forepaw treading was increased 20-fold after co-treatment with the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). DOI induced head twitches which were inhibited by 8-OHDPAT. The putative ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90178-7
更新日期：1989-02-14 00:00:00
abstract：:This work investigates the actions of LASSBio-1289, (E)-N-methyl-N'-(thiophen-3-methylene)benzo[d][1,3]dioxole-5-carbohydrazide, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Two weeks following the MCT injection, LASSBio-1289 (50 or 75mg/kg, p.o.) or vehicle was administrated once dail...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.01.050
更新日期：2013-02-28 00:00:00
abstract：:Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.06.029
更新日期：2017-10-05 00:00:00
abstract：:The release of endogenous aspartic acid (Asp), glutamic acid (Glu) and gamma-aminobutyric acid (GABA) was investigated in synaptosomes prepared from various regions of the rat brain. The basal release of Asp, Glu and GABA from various regions was 12-35, 24-107 and 15-43 pmol/min per mg protein, respectively. Exposure ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90511-2
更新日期：1992-06-24 00:00:00
abstract：:The relationship between morphine tolerance and pituitary-adrenocortical activity was examined. In rats made tolerant to morphine by implantation of morphine-containing pellets, there was a significant reduction in plasma levels of beta-endorphin-like immunoreactivity (beta-END-LI), whereas no significant changes in c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90499-v
更新日期：1990-06-21 00:00:00
abstract：:Malfunction of the serotonergic system and dysregulation of the hypothalamo-pituitary-adrenocortical axis have been implicated in the pathophysiology of depression. Several studies provide evidence for reciprocal influences between glucocorticoids and 5-HT receptors. The effect of repeated treatment with a high dose o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00286-5
更新日期：1996-07-18 00:00:00
abstract：:The administration of the dopamine D-1 receptor antagonist, SCH 23390, but not of the dopamine D-2 receptor antagonist, sulpiride, suppressed the excessive grooming induced by a new environment or by various neuropeptides. In addition, administration of the dopamine D-1 agonist, SK & F 38393, induced excessive groomin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90527-x
更新日期：1989-12-07 00:00:00
abstract：:Intrastriatal injection of kainic acid (5 nmoles) to rats led to severe destruction of nerve cell bodies throughout the caudate-putamen complex and an extensive proliferation of glial cells. Lesioned striata displayed a significant 23% loss of beta-adrenoceptor binding sites 21--24 days after injection of kainic acid....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90226-7
更新日期：1979-12-07 00:00:00
abstract：:Primary cultures of rat cerebellar granule neurons express 5-lipoxygenase, an enzyme from the inflammatory pathway of arachidonic acid. Outside the central nervous system (CNS) 5-lipoxygenase participates in cell proliferation. We hypothesized that 5-lipoxygenase is needed for proliferation of immature cerebellar gran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00924-4
更新日期：2001-04-20 00:00:00
abstract：:The ontogenesis of kappa-opioid receptors has been studied in the postnatal period from day 5 to day 30 using the highly selective kappa-site ligand [3H]U-69593 in binding studies. Analyses of saturation curves revealed a marked increase in the binding capacities between day 5 and day 10 with no further increment in t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90157-2
更新日期：1990-01-03 00:00:00
abstract：:The present study was an attempt to answer the question whether the local anesthetic [3H]tetracaine labels sodium channels in mouse brain synaptosomes. Binding of [3H]tetracaine had a Kd of 0.19 microM and a Bmax ranging from 3.7 to 5.2 pmol/mg of protein. Local anesthetics other than tetracaine and cocaine-related co...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90530-9
更新日期：1987-11-10 00:00:00
abstract：:Thapsigargin (TG), an inhibitor of Ca(2+) ATPase pumps in the endoplasmic reticulum (ER), inhibits replication of human vascular smooth muscle cell (hVSMC) at low nM concentrations. TG blocks replication of other cell types through promotion of ER stress (ERS). In order to determine whether ERS may mediate the cytosta...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.05.036
更新日期：2013-08-15 00:00:00
abstract：:We are interested in the rat as an animal model for infant-mother attachment. In the first experiment we tried to distinguish between a preference for familiar animals (attachment theory) and a preference for genetically related animals (kin selection theory) with the use of an early cross-fostering procedure. Genetic...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.03.070
更新日期：2009-06-10 00:00:00
abstract：:The mechanism by which dibutyryl cyclic AMP (db-cAMP) induces vasodilatation was examined in isolated rat aorta. The contraction induced by norepinephrine (NE) was more sensitive to the inhibitory effect of db-cAMP than that induced by high K+, and the contraction induced by lower concentrations of each stimulant was ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90385-h
更新日期：1992-02-18 00:00:00
abstract：:CPP has a potent anticonvulsant effect against sound-induced seizures in audiogenic DBA/2 mice. Pretreatment with CPP (0.01-10 nmol i.c.v., 45 min) protects against successive phases of sound-induced seizures in a dose-dependent fashion (ED50, tonic phase, 0.023 nmol; clonic phase, 0.039 nmol; wild running, 0.17 nmol)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90501-2
更新日期：1987-07-02 00:00:00
abstract：:The influence of increasing concentrations of histamine (0.1 microM-1 mM) was studied on proximal and distal ring segments of left anterior descendens coronary arteries isolated from rats. Addition of histamine to prostaglandin F2 alpha (10 microM)-precontracted proximal segments elicited a further contraction. This e...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90259-3
更新日期：1994-12-12 00:00:00
abstract：:[3H]Rauwolscine, a specific and potent alpha 2-antagonist radioligand, was used to characterize alpha 2-receptor binding in bovine cerebral cortex. [3H]Rauwolscine binding was reversible, stereospecific, and saturable. Association, dissociation, and saturation studies revealed one site interactions (k -1/k+1 = 1.2 nM,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90123-0
更新日期：1981-12-17 00:00:00
