Abstract：
:Current clinical options for the treatment of neovascular disorders of the posterior segment of the eye have several drawbacks. Photocoagulation lasers can impair peripheral and night vision. Photodynamic therapies as well as intravitreal macromolecule injections (Macugen and Lucentis) require frequent, invasive administrations. Above all, only modest improvement in vision is achieved with any of the existing treatments. In order to overcome these limitations in the long run, this study investigated the antiangiogenic potential of AQ4, a low molecular weight anthracenedione. The results indicate that AQ4 enters the cell nucleus and inhibits proliferation of choroid-retina endothelial (RF/6A) cells and human retinal pigment epithelial (ARPE-19) cells under hypoxic (1% O(2)) as well as normoxic (21% O(2)) conditions. The IC(50) for these effects ranges from 5.5 to 6.9 muM. AQ4 does not affect the viability of non-dividing RF/6A or ARPE-19 cells up to 0.1 mM. Further, AQ4 (20 muM) reduces vascular endothelial growth factor (VEGF) protein secretion by about 50% in ARPE-19 cells under normoxia as well as hypoxia, possibly by reducing VEGF transcription. AQ4 arrests the growth of endothelial cells in S phase, consistent with interference of AQ4 with DNA replication. These results for the first time suggest that AQ4 can potentially alleviate the neovascularization of choroid/retina by a dual mechanism of inhibiting the proliferation of endothelial cells and by reducing mitogenic VEGF stimulus from retinal pigment epithelial cells.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Raghava S,Kompella UBdoi
10.1016/j.ejphar.2007.04.044subject
Has Abstractpub_date
2007-07-30 00:00:00pages
68-74issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(07)00506-7journal_volume
568pub_type
杂志文章abstract：:In pentobarbital (35.0 mg/kg) anaesthetised dogs, bolus injections of prazosin into the femoral artery (3.0--300.0 microgram) provoked a dose-related fall in the vascular resistance of the innervated hind limb. In contrast to papaverine, prazosin failed to produce the same effect in dogs under spinal anaesthesia even ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90101-2
更新日期：1978-06-01 00:00:00
abstract：:The effects of P2Y receptor agonists on smooth muscle membrane potential in isolated ring segments of rat mesenteric artery were examined by intracellular microelectrodes. In the presence of inhibitors of nitric oxide-synthase and cyclo-oxygenase, the selective P2Y1 receptor agonist adenosine 5'-O-thiodiphosphate (ADP...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00848-6
更新日期：1999-01-08 00:00:00
abstract：:Drugs differentially affecting catecholaminergic neurotransmission mechanisms were injected into isolated mice to assess effects on aggression. L-DOPA in combination with a peripheral decarboxylase inhibitor produced a dose-dependent decrease in the number of fights and average fight durations accompanied by an increa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90081-3
更新日期：1975-03-01 00:00:00
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90628-h
更新日期：1992-03-31 00:00:00
abstract：:After incubation of rat cortical cell cultures with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 12 h, cells showed fragmentation of DNA at internucleosomal linkers, the characteristic feature of apoptosis. In a quantitative approach, it was determined that the percentage of DNA fragmentation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(92)90063-2
更新日期：1992-07-01 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)90520-0
更新日期：1986-11-12 00:00:00
abstract：:The adenosine-receptor modulation of noradrenaline release was compared in prostatic and epididymal portions of rat vas deferens. In both portions, tritium overflow elicited by electrical stimulation (100 pulses/8 Hz) was reduced by the adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine, and enhanced by the no...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01906-4
更新日期：2002-07-12 00:00:00
abstract：:Membrane preparations of guinea-pig lung (containing multiple muscarinic receptor subtypes) and heart (containing M2 receptors only) were incubated with either neuraminidase, parainfluenza virus (which contains neuraminidase), or virus plus 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, a neuraminidase inhibitor. None o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90244-z
更新日期：1990-05-31 00:00:00
abstract：:Macrophages play important roles in the healing and remodeling of cardiac tissues after myocardial ischemia/reperfusion (MI/R) injury. Here we investigated the potential effects of salvianolic acid B (SalB), one of the abundant and bioactive compounds extracted from Chinese herb Salvia Miltiorrhiza (Danshen), on macro...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172916
更新日期：2020-03-15 00:00:00
abstract：:Angiogenesis is critical for re-establishing blood supply to the ischemic myocardium after acute myocardial infarction (AMI). This study aimed to investigate the effects of morroniside on angiogenesis after AMI and explored associated proangiogenic mechanisms. A rat model of AMI was established by ligation of the left...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172954
更新日期：2020-04-05 00:00:00
abstract：:Guanosine 3',5'-cyclic monophosphate (cGMP) is an important second messenger in many biological systems including vascular smooth muscle where it mediates relaxation. Cellular levels of cGMP are regulated primarily by three enzymes; nitric oxide (NO) synthase, soluble guanylate cyclase, and cGMP-phosphodiesterase. Bas...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00307-0
更新日期：1998-06-19 00:00:00
abstract：:Amphetamine increases extracellular dopamine and induces locomotor and stereotypical behaviors in rats. This study examined the effect of the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg s.c.) on the dopaminergic response to amphetamine (0.5, 2.0, or 8.0 mg/kg i.p.) in male Sprague-Dawley rats. Extracellular...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00936-0
更新日期：2001-04-27 00:00:00
abstract：:Several studies have recently suggested a principal role of adenosine in the pathogenesis of radiocontrast media-induced nephropathy. In the present experiments, we therefore investigated the renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a potent and selective adenosine A1 receptor ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00764-6
更新日期：2001-02-23 00:00:00
abstract：:We investigated protein kinase C participation in the contractile response to 5-hydroxytryptamine (5-HT), and in the interaction between 5-HT and endothelin-1, in aortas from control and diabetic rats. Diabetic rats display attenuated reactivity to 5-HT (i.e., approximately 47% of control maximum). The protein kinase ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00986-7
更新日期：1997-03-12 00:00:00
abstract：:The pharmacological treatment of mood and anxiety disorders has for long relied on the serendipitous findings of monoaminergic and benzodiazepine drugs more than 50 years ago. These treatments, however, are therapeutically insufficient and even though more recently developed drugs are particularly improving side effec...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2008.01.057
更新日期：2008-05-13 00:00:00
abstract：:Vascular tissue consists of endothelial cells, vasoactive smooth muscle cells and perivascular nerves. The perivascular sensory neuropeptide CGRP has demonstrated potent vasodilatory effects in any arterial vasculature examined so far, and a local protective CGRP-circuit of sensory nerve terminal CGRP release and smoo...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.173205
更新日期：2020-08-15 00:00:00
abstract：:As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat bladder dome. The density of endothelin receptors in the rat bladder dome was higher (8 and 16 weeks f...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00753-0
更新日期：2000-01-17 00:00:00
abstract：:In preceding papers, we proposed that procainamide hydrochloride, a class I antiarrhythmic agent, was able to protect mice and rats from cisplatin-induced nephrotoxicity and that it could exert its action through accumulation in kidneys followed by coordination with cisplatin (or its hydrolysis metabolites) and format...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01537-6
更新日期：2002-05-10 00:00:00
abstract：:We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we fur...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.03.023
更新日期：2012-05-15 00:00:00
abstract：:Brain microvessel endothelial cell monolayers have been shown to be a suitable blood-brain barrier in vitro system to study adrenergic regulation of permeability. We tested adrenergic drugs on bovine brain microvessel endothelial cell monolayer permeability to a biomembrane impermeant molecule, sodium fluorescein. End...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90092-2
更新日期：1994-10-14 00:00:00
abstract：:Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the imp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.06.008
更新日期：2015-09-05 00:00:00
abstract：:Swallowing is a patterned motor activity generated by neurons located within the nucleus tractus solitarii (NTS). Previous experiments have shown that administration of excitatory amino acids within the NTS induces swallowing. The present study was undertaken to identify the receptor subtypes involved in this effect. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90323-i
更新日期：1991-08-16 00:00:00
abstract：:Osteoporosis is a reduction in skeletal mass due to an imbalance between bone resorption and bone formation. Bone morphogenetic protein (BMP) plays important roles in osteoblastic differentiation and bone formation. Therefore, components involved in BMP activation are good targets for the development of anti-osteoporo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.10.013
更新日期：2008-01-28 00:00:00
abstract：:The cGMP response and the accumulation of inositol monophosphate (IP) induced by carbachol were compared in slices of different rat brain structures. Basal cGMP and the responses of cGMP to carbachol appeared dependent on the concentration of added Ca2+, suggesting that distinct Ca(2+)-mediated and Ca(2+)-sensitive mu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(91)90029-h
更新日期：1991-07-12 00:00:00
abstract：:Acute kidney injury (AKI) is defined as a rapid loss of kidney function characterised by inflammation and cell death, ultimately leading to further functional and structural renal alterations. Based on experimental and epidemiological pieces of evidence, AKI may progress to chronic kidney disease (CKD) even after a re...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.172711
更新日期：2019-12-15 00:00:00
abstract：:The acetylcholine receptor agonists, acetylcholine (10(-5)-10(-4 M), carbachol (5 x 10(-6)-5 x 10(-5) M), bethanechol (5 x 10(-5)-5 x 10(-4) M) and dimethylphenylpiperazinium (DMPP, 10(-5) M) increased the short-circuit current (Isc) in the rat colon descendens by a tetrodotoxin (TTX)-sensitive mechanism. Blockade by ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90568-2
更新日期：1989-09-13 00:00:00
abstract：:Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentrations of ApoB or LDL. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.01.008
更新日期：2014-02-15 00:00:00
abstract：:Excitotoxicity and imbalance of sodium and calcium homeostasis trigger pathophysiologic processes in cerebral ischemia which can accelerate neuronal death. Neuroprotective role of cannabidiol (CBD), one of the main non-psychoactive phytocannabinoids of the cannabis plant, has attracted attention of many researchers in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.11.011
更新日期：2017-01-05 00:00:00
abstract：:Repeated morphine treatments result in sensitization, an increase in the efficacy of morphine to stimulate locomotor activity. study examined the effects of increasing serotonin (5-hydroxytryptamine, 5-HT) transmission on morphine-sensitization. For five days rats were administered saline or 5.0 mg/kg fluoxetine prior...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01308-3
更新日期：1997-10-22 00:00:00
