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["(propoxy),7'(4-morpholino)-phenacyl],[1-methyl-3 propyl]pyrazolo[4,3d]pyrimidin-7-one), has been described to be a very potent cGMP-specific phosphodiesterase inhibitor. In the present study, we compared the potency of GF248 and other known cGMP-specific phosphodiesterase inhibitors on phosphodiesterase 5 and phosphodiesterase 6. GF248 displayed an IC50 of 2 and 5 nM for phosphodiesterase 5 and phosphodiesterase 6, respectively. Thereafter, we assessed the effect of GF248 on retinal function, using an ex vivo model of isolated retina electroretinogram recording. Exposure of retina to GF248 resulted in a dose-dependent decrease in electroretinogram amplitude (PIII and b-waves), with no marked modification of PIII and b-wave implicit time. Among other phosphodiesterase inhibitors, DMPPO (1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazol ol[3,4d]-pyrimidin-4-(5H)-one) and dipyridamole, cGMP-specific phosphodiesterase inhibitors, and IBMQ (1-isobutyl-3-methylimidazol[1,5a]quinoxalin-4-(5H)one), a nonselective phosphodiesterase inhibitor, altered retinal function but less potently than GF248, consistent with their in vitro phosphodiesterase 6 inhibition. Phosphodiesterase 3- and phosphodiesterase 4-selective inhibitors, cilostamide and rolipram, respectively, did not affect retinal function at 10 micromol l(-1). Our conclusion from these data is that GF248, a potent phosphodiesterase 6 inhibitor, could interfere with visual transduction by cGMP accumulation.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Estrade M,Grondin P,Cluzel J,Bonhomme B,Doly Mdoi
10.1016/s0014-2999(98)00346-xsubject
Has Abstractpub_date
1998-07-10 00:00:00pages
157-63issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(98)00346-Xjournal_volume
352pub_type
杂志文章abstract：:The effects of indapamide on contractile responses in various isolated artery rings and on spontaneous mechanical activity in portal vein segments were investigated. Arteries used were: rabbit aorta, mesenteric (fifth branch), femoral and basilar, and sheep coronary arteries. 45Ca2+ uptake was also analysed in rabbit ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90630-z
更新日期：1993-11-30 00:00:00
abstract：:[3H]MDL 105,519 (((E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1[3H]-indole-2-ca rboxylic acid) is a novel radioligand which binds with high affinity, Kd = 2.5 nM, to the glycine site of adult rodent forebrain, N-methyl-D-aspartate subtype of glutamate receptors. As with other glycine site antagonists, the major det...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00431-2
更新日期：1998-07-17 00:00:00
abstract：:Several phenyl-benzazepine compounds, putatively selective dopamine D1 receptor agonists, have been used to study the effects of dopamine D1 receptor stimulation in rodents and nonhuman primates. However, the dopamine receptor selectivities of these compounds have not been established in nonhuman primates. Accordingly...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00669-4
更新日期：1998-11-13 00:00:00
abstract：:Calcitonin can selectively modulate the effects of opioids on the rat hypothalamic-pituitary-adrenal axis and increase the release of corticosterone induced by a kappa-opioid receptor agonist. Considerable evidence supports the involvement of opioid and serotonergic systems in the analgesic effect of calcitonin. In th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01355-1
更新日期：1997-12-04 00:00:00
abstract：:Cultured chick hepatocytes were used to investigate the hepatotoxicity of methotrexate alone and in combination with paracetamol. Treatment with methotrexate alone at concentrations as high as 1 mg/ml resulted in no toxicity in cultured chick hepatocytes, as indicated by no detachment of cells and no effect on protein...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(93)90063-v
更新日期：1993-04-01 00:00:00
abstract：:The coronavirus disease-19 (COVID-19) outbreak that is caused by a highly contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a zoonotic pandemic, with approximately 24.5 million positive cases and 8.3 lakhs deaths globally. The lack of effective drugs or vaccine provoked the research fo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173688
更新日期：2021-01-05 00:00:00
abstract：:The aim of the present study was to determine whether U50,488H (a selective kappa-opioid receptor agonist) inhibits cardiac hypertrophy and fibrosis induced by beta-adrenoceptor stimulation in a rat model. Cardiac hypertrophy and fibrosis were developed by intraperitoneal administration of isoprenaline (ip. 3.0 mg/kg/...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.01.050
更新日期：2009-04-01 00:00:00
abstract：:Male mice from 14 strains were injected i.p. with tremorine (3.0 mg/kg) or oxotremorine (0.15 or 0.1 mg/kg). Large inter-strain differences in the degree and duration of the subsequent hypothermia were noted. 2 strains, BALB/c and Simpson, were particularly sensitive to the hypothermic effect of oxotremorine. The offs...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90226-1
更新日期：1978-05-01 00:00:00
abstract：:Based on the ability of many receptors to amplify NIH 3T3 cells, we developed a high throughput assay of cloned receptor pharmacology. In this assay, receptors are transiently co-expressed with the marker enzyme beta-galactosidase. Receptors that induce cellular proliferation select and amplify the cells that also exp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00639-7
更新日期：1996-01-04 00:00:00
abstract：:The new dihydropyridine calcium channel antagonist S 11568 and its optical isomers, S 12967 and S 12968 (3 x 10(-6) to 10(-4) M), caused, unlike nifedipine (10(-4) M), equipotent and rapid endothelium-dependent relaxations and increased the content of cyclic GMP in rings of canine femoral arteries. These effects were ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90362-t
更新日期：1991-05-02 00:00:00
abstract：:Studies were designed to examine the influence of endothelin type A receptor (ETA) blockade on the hypertensive and renal response to 4 day treatment with the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME), and cyclosporine. In the first series of experiments, male Sprague-Dawley rats main...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00043-0
更新日期：1998-04-03 00:00:00
abstract：:Chlorin derivatives have been known for their biological activities. Especially due to their advanced electron transfer capacity they have been used as photodynamic therapy agent both at clinical and laboratory scales. Photodynamic therapy (PDT) against cancer or an infectious disease aims the development of less side...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172980
更新日期：2020-04-15 00:00:00
abstract：:Mitochondria play a central role in cell biology not only as producers of ATP, but also in the sequestration of Ca(2+) and the generation of free radicals. They are also repositories of several proteins which regulate apoptosis. Perturbations in the normal functions of mitochondria will inevitably disturb cell functio...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(02)01842-3
更新日期：2002-07-05 00:00:00
abstract：:Effects of (2RS, 3SR)-2-aminomethyl-2,3,7,8-tetrahydro-2,3,5,8, 8-pentamethyl-6H-furo-[2,3-e] indol-7-one hydrochloride (UK-1745), a novel cardiotonic drug with beta-adrenoceptor blocking property and antiarrhythmic activity, on the action potentials of isolated papillary muscles and the membrane currents of single ve...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00651-2
更新日期：1999-11-03 00:00:00
abstract：:Previous studies show that naringenin promotes insulin sensitivity in fructose-fed rats. This study investigates whether naringenin prevents oxidative events and apoptotic changes triggered in the rat liver by a high fructose diet. Male Wistar rats of body weight 150-180 g were fed either diet containing starch (60% c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.07.015
更新日期：2010-10-25 00:00:00
abstract：:Patients with somatic mutations of epigenetic regulators are characterized by aberrant chromatin modification patterns. Recent mechanistic studies pairing chemical tool compounds and deep-sequencing technology have greatly broadened our understanding of epigenetic regulation in glioma progression and underpinned alter...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2018.05.047
更新日期：2018-08-15 00:00:00
abstract：:We have previously reported that 15-hydroxyeicosatetraenoic acid (15-HETE), a metabolite of arachidonic acid by 15-lipoxygenase, causes pulmonary vasoconstriction via increasing the intracellular Ca(2+) concentration ([Ca(2+)]i). However, the multiple sources of Ca(2+) that contribute to Ca(2+) elevation during and af...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.10.028
更新日期：2008-12-28 00:00:00
abstract：:A microcomputer-based system has been used to apply the technique of excitability testing to the study of the actions of a range of pharmacological agents on the excitability of single primary afferent terminals in the mouse spinal cord in vitro. GABAA analogues all evoked increases in excitability that were bicuculli...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90554-1
更新日期：1987-09-23 00:00:00
abstract：:In the presence of l-serine borate, salbutamol was much more effective in reversing rather than preventing LTC4-induced contractions of guinea-pig trachea. This suggests that different mechanisms are involved in initiating versus maintaining LTC4-induced contractions. In addition, the ability of salbutamol pretreatmen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90066-x
更新日期：1986-07-31 00:00:00
abstract：:Clonidine and other imidazolines, including phentolamine, inhibited the norepinephrine-elicited accumulation of cyclic AMP in brain slices via blockade or postsynpatic alpha-adrenoceptors. Clonidine (0.0125--0.050 mg/kg, i.p.) antagonized the increase in locomotor activity induced by amphetamine in a dose-dependent ma...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90126-7
更新日期：1978-02-15 00:00:00
abstract：:Infusion of tryptamine (1-4 mug/ml) through the pulmonary circulation of rat isolated lung perfused with Krebs solution caused release of a mixture of spasmogens contracting isolated smooth muscle preparations. One component of this mixture had biological activity comparable to E-type prostaglandins. Other components ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90238-7
更新日期：1976-02-01 00:00:00
abstract：:Cytotrienin A, a member of the triene-ansamycin family, was initially identified to be an inducer of apoptosis and recently shown to be an inhibitor of translation that interferes with eukaryotic elongation factor 1A function. In human lung carcinoma A549 cells, cytotrienin A was found to inhibit more strongly the cel...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.05.072
更新日期：2011-09-30 00:00:00
abstract：:Plants are a natural source of bioactive compounds such as secondary metabolites. These molecules, also called phytochemicals, are fundamental for plant survival and often show therapeutic properties used for the treatment of human diseases. Asperuloside is a secondary metabolite which belongs to iridoid glycosides an...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.173344
更新日期：2020-09-15 00:00:00
abstract：:To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90023-8
更新日期：1985-03-26 00:00:00
abstract：:The antagonistic effects of a new inositol phosphate derivative, D-myoinositol-1,2,6-trisphosphate (PP56), on pressor responses to preganglionic sympathetic nerve stimulation and exogenously administered phenylephrine or neuropeptide Y (NPY) were investigated in vivo in the pithed rat. In this model an intravenous (i....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90853-i
更新日期：1991-11-12 00:00:00
abstract：:Previous studies have shown that treatment of guinea-pig isolated vas deferens with the affinity label periodate-oxidized ATP (2',3'-dialdehyde ATP), results in two irreversible effects on biphasic contractile responses to ATP, i.e., potentiation of the P2X purinoceptor-mediated first phase and inhibition of the ecto-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00352-l
更新日期：1995-08-04 00:00:00
abstract：:Bitter taste receptors (Tas2rs) initiate a bitter taste signaling involving the activation of taste-specific G protein gustducin and phosphodiesterases (PDEs); it leads to the decrease of cytosolic level of cyclic adenosine monophosphate (cAMP) in taste cells. Recent studies have identified the expression of Tas2rs in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172951
更新日期：2020-04-05 00:00:00
abstract：:Germacrone is one of the main bioactive components in the traditional Chinese medicine Rhizoma curcuma. In this study, the anti-proliferative effect of germacrone on the human hepatoma cell lines and the molecular mechanism underlying the cytotoxicity of germacrone were investigated. Treatment of human hepatoma cell l...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.10.013
更新日期：2013-01-05 00:00:00
abstract：:Recent studies have suggested that hydrogen sulfide (H2S), an important endogenous signaling gaseous molecule, participates in relaxation of smooth muscle. Nevertheless, the mechanism of this relaxation effect on respiratory system is still unclear. The present study aims to investigate the physiological function as w...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.07.004
更新日期：2014-10-15 00:00:00
abstract：:Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the hos...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.02.008
更新日期：2014-04-15 00:00:00
