Abstract：
:The aims of the present study were to examine the effect of adenosine monophosphate-activated protein kinase (AMPK) activation on airway smooth muscle cells (ASMCs) proliferation and to address its potential mechanisms. Platelet derived growth factor (PDGF) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, and this in turn up-regulated S-phase kinase-associated protein 2 (Skp2) and consequently reduced cyclin dependent kinase inhibitor 1B (p27) leading to ASMCs proliferation. Pre-incubation of cells with metformin, an AMPK activator, blocked PDGF-induced activation of mTOR and its downstream targets changes of Skp2 and p27 without changing Akt phosphorylation and inhibited ASMCs proliferation. Transfection of ASMCs with AMPK α2-specific small interfering RNA (siRNA) reversed the effect of metformin on mTOR phosphorylation, Skp2 and p27 protein expression and cell proliferation. Our study suggests that activation of AMPK, particularly AMPK α2, negatively regulates mTOR activity to suppress ASMCs proliferation and therefore has a potential value in the prevention and treatment of asthma by negatively modulating airway remodeling.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Liu L,Pan Y,Song Y,Su X,Ke R,Yang L,Gao L,Li Mdoi
10.1016/j.ejphar.2016.09.003subject
Has Abstractpub_date
2016-11-15 00:00:00pages
235-243eissn
0014-2999issn
1879-0712pii
S0014-2999(16)30563-5journal_volume
791pub_type
杂志文章abstract：:The putative dopamine (DA) autoreceptor agonists, N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) and 6, 7-dihydroxy-2-dimethylaminotetralin (TL-99) were compared with apomorphine in a series of tests indicative of DA receptor activation. All three agents displaced [3H] apomorphine and [3H] spiroperidol from DA reco...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90004-2
更新日期：1981-11-19 00:00:00
abstract：:Tricyclic antidepressants have analgesic and sedative effects in addition to their antidepressive properties. We tested the acute analgesic and locomotor inhibitory effects of the tricyclic antidepressant amitriptyline and the alpha(2)-adrenoceptor agonist clonidine in wild-type control and in alpha(2A)-adrenoceptor k...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.11.047
更新日期：2004-02-06 00:00:00
abstract：:The steady-state levels and utilization (alpha-MPT-induced disappearance) of noradrenaline (NA) and dopamine (DA) were measured in distinct mouse brain nuclei after acute morphine challenge, in mice rendered tolerant to morphine, and during the naloxone-precipitated morphine withdrawal syndrome. Mouse brain nuclei con...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90132-2
更新日期：1983-09-30 00:00:00
abstract：:EMD 57445 ((S)-(-)-[4-hydroxy-4-(3,4-benzodioxol-5-yl) -piperidin-1-ylmethyl]-3-(4-methoxyphenyl)-oxazolidin- 2-one) is a new sigma receptor ligand with only marginal affinity for many other (including dopamine) receptors. In the present study, central, particularly neuroleptic-like, effects of this compound were eval...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00602-4
更新日期：1996-11-21 00:00:00
abstract：:[3H]Idazoxan is a labelled ligand that is frequently used to study alpha 2-adrenoceptors in the central nervous system. In pig kidney membranes, [3H]idazoxan labelled high-affinity binding sites (Kd = 1.5 nM) that were not alpha 2-adrenoceptors and which recognized clonidine with low affinity. This new class of bindin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90503-7
更新日期：1989-01-31 00:00:00
abstract：:We have investigated the mode of cardiovascular action of the stimulant methylhexaneamine (MHA) in terms of direct or indirect adrenergic actions in anaesthetised rats. Male and female rats were anaesthetised with pentobarbitone and pressor (changes in diastolic blood pressure) and cardioaccelerator responses to MHA w...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.10.047
更新日期：2019-01-15 00:00:00
abstract：:Dysfunction of the innate immune system has been reported to cause intestinal inflammation. Vitamin D3 is known to be an important immune system regulator and exerts anti-inflammatory effects. We investigated in vitro effects of vitamin D3 and its derivatives on the innate immune system in HT-29 cells, a line of human...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.09.014
更新日期：2013-12-05 00:00:00
abstract：:The effects of morphine (0.1 mg/kg) and 5-HTP (2 mg/kg) on colonic motility were investigated in dogs fasted for 15-22 h and fitted with two strain gauge transducers on the transverse colon at 8 and 12 cm from the ileo-colonic junction. The effects were compared to those obtained after previous intravenous (i.v.) (0.2...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90503-9
更新日期：1982-08-27 00:00:00
abstract：:In rat carotid arteries isolated 2 weeks after balloon denudation, a significant neointima developed with little change in medial size. Associated with this neointimal hyperplasia was a marked decrease in contraction to various agents including angiotensins I and II, big endothelin-1, endothelin-1, norepinephrine, phe...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90610-6
更新日期：1994-04-11 00:00:00
abstract：:Our aim was to investigate the role of oxidative stress and inflammation on the functional and biochemical changes caused by hyperglycemia in the aorta and corpus cavernosum tissues of streptozotozin diabetic rats and to determine if rosiglitazone and/or insulin treatment has any preventive effect on organ dysfunction...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.03.030
更新日期：2011-06-25 00:00:00
abstract：:Rolipram was characterized for its emetic, behavioral, cardiovascular and pulmonary activities in dogs, to assess its systemic pharmacology and potential bronchodilatory selectivity. At doses > or = 0.1 mg/kg i.v., rolipram induced emesis, anxiety, and stepping behaviors in conscious dogs, and increased heart rate and...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00457-2
更新日期：1995-11-24 00:00:00
abstract：:Three naturally occurring peptides, pGlu-Glu-Pro amide, pGlu-Phe-Pro amide and pGlu-Gln-Pro amide, with similar structures to thyrotropin releasing hormone (TRH) have recently been identified but no studies of their in vivo activities have been reported previously. We describe here the ability of pGlu-Phe-Pro amide an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00593-7
更新日期：1998-09-25 00:00:00
abstract：:High pressure liquid chromatography (HPLC) combined with radiochemical detection was used to show that [3H]noradrenaline (NA) and [14C]ATP were released concomitantly during field stimulation of the rat vas deferens. The release of radioactivity (3H and 14C) in response to three consecutive field stimulations was cons...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90254-3
更新日期：1988-12-06 00:00:00
abstract：:Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-gal...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.12.006
更新日期：2016-01-05 00:00:00
abstract：:Recombinant human tumor necrosis factor alpha (TNF alpha) decreases social exploration and induces weight loss in mice in a dose- and time-dependent manner (2.5-40 micrograms/mouse). To assess the role of interleukin-1 (IL-1) in these effects, mice pretreated with IL-1 receptor antagonist (IL-1ra, 500 micrograms/mouse...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90184-r
更新日期：1991-12-17 00:00:00
abstract：:The ability of SCH 23390 as compared to haloperidol to produce catalepsy in rats was evaluated in three tests for catalepsy. SCH 23390 produced catalepsy in all three tests with ED50 (mg/kg s.c.) of 0.017 on the vertical grid, 0.023 on the horizontal bar and 0.038 on the 'four corks'. Haloperidol produced catalepsy wi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90602-8
更新日期：1985-11-05 00:00:00
abstract：:The effect of cyclo-oxygenase inhibitors, indomethacin and nimesulide, on the action of i.v. morphine on dopamine neurons projecting to the nucleus Accumbens was studied using standard extracellular recording techniques coupled with antidromic identification in unanesthetized rats. The i.v. administration of either ni...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00799-2
更新日期：2000-01-03 00:00:00
abstract：:Phenoxybenzamine greatly attenuated phenylephrine-induced contractions of dog saphenous vein in vitro, but had less effect on contractions induced by clonidine. The phenoxybenzamine-resistant responses to clonidine were not affected by prazosin or by corynanthine but were competitively antagonized by yohimbine (pA2 8....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90219-9
更新日期：1982-12-03 00:00:00
abstract：:Clopidogrel is not safe enough for the gastric mucosa in patients with high risk of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats and the ulcer size, mucosal epithelial cell proliferation of the ulcer margi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.07.054
更新日期：2012-11-15 00:00:00
abstract：:Cytokines and cytokine-induced nitric oxide (NO) play important roles in inflammatory glomerular diseases, and both platelet-derived growth factor and transforming growth factor-beta inhibit cytokine-induced NO production. In this study, we demonstrated that a selective endothelin ET(A) receptor antagonist, BQ-485 (He...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00849-8
更新日期：1999-01-15 00:00:00
abstract：:Pieces of rat brain incubated in oxygenated Tyrode solution were stimulated with the divalent cation ionophore A 23187. Incubation media were assayed for leukotriene (LT) C4-like immunoreactivity as well as for prostaglandin (PG) D2, 6-keto-PGF1 alpha and thromboxane (TX) B2 using specific and sensitive radioimmunoass...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90431-x
更新日期：1984-03-16 00:00:00
abstract：:We tested the hypothesis that calcium from the sarcoplasmic reticulum contributes to exercise-induced muscle damage. Dantrolene sodium (Dantrium) is a muscle relaxant that affects the flux of calcium over the sarcoplasmic membrane. Rats were treated with dantrolene sodium for a week before a 2 h run on a treadmill. We...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90417-5
更新日期：1990-04-10 00:00:00
abstract：:The impairment of arterial baroreceptor and vasodilator functions are two major contributors to the hypertensive action of cyclosporine (CSA). In this study, in vivo and in vitro pharmacological studies were performed to investigate whether these effects of CSA are differentially modulated by endothelin and thromboxan...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.01.034
更新日期：2014-03-15 00:00:00
abstract：:Lipopolysaccharide (LPS) administration in rats induces a characteristic syndrome termed 'sickness behavior', including profound changes on locomotor activity and circulating stress and inflammatory mediators. The aim of the present investigation was to evaluate whether the behavioral and the peripheral biomarker resp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.04.020
更新日期：2011-07-01 00:00:00
abstract：:Experiments were conducted to explore the effects of Neuropeptide FF acting at spinal and supraspinal sites in models of chronic inflammatory or neuropathic pain and of acute pain. Neuropeptide FF was administered intrathecally (i.t.; 10.0, 25.0 and 50.0 nmol) or intracerebroventricularly (i.c.v.; 10.0, 12.5 and 15.0 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00668-3
更新日期：2000-11-03 00:00:00
abstract：:A recent study indicates that elevation of [Ca(2+)](i) enhances the release of calcein, an anionic fluorescent dye, from isolated exocrine acinar cells, so cytoplasmic calcein is useful for monitoring the secretion of organic anions. In this study, we investigated the effect of cAMP on the calcein release evoked by el...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00898-5
更新日期：2000-02-04 00:00:00
abstract：:The administration of [D-Ala2,Met5]enkephalinamide (D-AME) and [D-Ala2,Leu5]enkephalinamide (D-ALE) into the right atrium of decerebrate rats caused bradycardia, a slight transient biphasic blood pressure response and apnea within 1-2 sec. Apnea was followed by rapid shallow breathing. These effects were dose related ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90372-7
更新日期：1982-02-19 00:00:00
abstract：:The ischemic stroke cascade is composed of several pathophysiological events, providing multiple targets for pharmacological intervention. JM-20 (3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido[2,3-b][1,5]benzodiazepine) is a novel hybrid molecule, in which a benzodiazepine portion is covalently lin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.01.021
更新日期：2014-03-05 00:00:00
abstract：:Bay k-8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro- methylphenyl)-pyridine-5-carboxylate) (a Ca2+ channel agonist of the dihydropyridine class) at 5 mg/kg (s.c.) impaired the anticonvulsant activities of two competitive NMDA receptor antagonists, CGP 37849 (D,L-(E)-2-amino-4-methyl-5-phosphono-3-penten...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90644-0
更新日期：1994-10-13 00:00:00
abstract：:Recent studies suggest that non-steroidal anti-inflammatory drugs have central sites of action which contribute to their analgesic efficacy. In the present study microinjections of the non-steroidal anti-inflammatory drug, dipyrone, were made into the medullary nucleus raphe magnus of lightly pentobarbital-anesthetize...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00909-0
更新日期：1996-12-27 00:00:00
