Abstract:
:We have studied the effects of selective and non-selective adenosine receptor agonists and antagonists in audiogenic-seizure-sensitive DBA/2 mice, an animal model of generalized reflex epilepsy. With the exception of the adenosine A3 receptor agonist, N6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (IB-MECA), all the agonists studied prevented the development of audiogenic seizures in a dose-dependent manner. The ED50 values against the clonic phase of the audiogenic seizures were low, that is: 0.06 mg/kg, i.p., for the adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), 0.02 and 0.03 mg/kg, i.p., for the adenosine A2A receptor agonists, 2-(4-(2-carboxyethyl)-phenylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) and 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2-HE-NECA), and 0.7 mg/kg, i.p., for the adenosine A1/A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA). Conversely, the non-selective agonist, N-ethyl-carboxamidoadenosine (NECA), was highly potent, the ED50 being 0.0005 mg/kg, i.p. In the absence of auditory stimulation, the adenosine receptor antagonists increased the incidence of both clonic and tonic seizures in DBA/2 mice. The ED50 values were: for caffeine, 207.5 mg/kg, i.p., for the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 327.8 mg/kg i.p., for the adenosine A2A receptor antagonists, 3,7-dimethyl-1-propylxanthine (DPMX), 86.7 mg/kg i.p., for the (E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837), 69.1 mg/kg i.p., and 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-(4,3-c)1,2,4-triazolo(1,5 -c)-pyrimidine (SCH 58261), 321.8 mg/kg i.p. The rank order of convulsant potency in our epileptic model, following intracerebroventricular administration, was DPCPX > DMPX > 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC) > KF 17837 > Caffeine > SCH 58261 > 5-amino-9-chloro-2-(2-furyl)-1,2,4-triazolo(1,5-c)quinazoline (CGS 15943). Following a subconvulsant audiogenic stimulus of 83 dB, all adenosine receptor antagonists induced both tonic and clonic seizures. The ED50 values for such proconvulsant effects were: for caffeine 0.04 mg/kg, i.p., for the adenosine A receptor antagonist, DPCPX, 5.84 mg/kg, i.p., for the adenosine A2A receptor antagonists, DMPX, 0.02 mg/kg, i.p., CGS 15943, 0.29 mg/kg i.p., KF 17837, 0.57 mg/kg, i.p., CSC 0.12 mg/kg, i.p. and SCH 58261 0.07 mg/kg, i.p., respectively. These data suggest that stimulation of adenosine A1 and A2A receptors is involved in the suppression of seizures.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
De Sarro G,De Sarro A,Di Paola ED,Bertorelli Rdoi
10.1016/s0014-2999(99)00132-6keywords:
subject
Has Abstractpub_date
1999-04-29 00:00:00pages
137-45issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(99)00132-6journal_volume
371pub_type
杂志文章abstract::β-Methoxyacrylate antibiotics are well known to inhibit the fungal and yeast mitochondrial respiratory chain. In addition, β-methoxyacrylates are reported to suppress the proliferation of mammalian cancer cells. Differentiation and cell-cycle arrest are closely related. The cell cycle of proliferating cells is suppres...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.08.018
更新日期:2012-11-05 00:00:00
abstract::The present work describes the mechanisms involved in the vasorelaxant effect of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Kaurenoic acid (10, 50 and 100 microM) concentration-dependently inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or -denuded rat aortic rings. Kau...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.04.003
更新日期:2004-05-25 00:00:00
abstract::Acoustic communication in male Chorthippus biguttulus is a suitable behavioral model to explore the physiological effects and underlying molecular mechanisms of identified neuropeptides. Proctolin plays a modulatory role in a neuronal circuit controlling sexual behavior in these insects. Activation of proctolin recept...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.08.010
更新日期:2009-10-01 00:00:00
abstract::Corticotropin releasing factor (CRF) is a hypothalamic hormone that also displays autocrine/paracrine roles at peripheral sites. High concentrations of CRF have been identified in endothelial cells and other inflammatory tissues. We investigated the effects of CRF and antagonists in the regulation of prostaglandin syn...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00416-6
更新日期:1998-07-24 00:00:00
abstract::Opiate tolerance is a critical issue in pain management. Previous studies show that activation of Mas-related gene (Mrg) C receptor can modulate the development of morphine tolerance. This study was designed to investigate the underlying mechanism(s). Intrathecal (i.t.) administration of morphine (20µg) increased the ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.10.011
更新日期:2017-11-15 00:00:00
abstract::The aims of the present study were to establish whether vasoactive intestinal polypeptide (VIP) could mobilize internally-stored Ca2+ and whether Ca2+ release could trigger Ca2+ influx from the extracellular space. Bovine pulmonary artery endothelial cells from an established cell line were loaded with fura-2/AM and c...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01315-0
更新日期:1997-11-27 00:00:00
abstract::The recent elucidation of the primary structures of different melatonin receptors as well as the deduction of the secondary structure of rhodopsin has allowed us to construct a model for melatonin recognition at its G protein-coupled receptor. To achieve this, we have used the quantum mechanics method Austin model 1 t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00114-8
更新日期:1996-05-23 00:00:00
abstract::We previously reported that glycoxidized low-density lipoprotein (glycoxidized LDL) enhanced monocyte chemoattractant protein-1 (MCP-1) mRNA expression through activation of nuclear factor-kappaB (NF-kappaB). Here we investigated the effects of dilazep, an anti-platelet agent, and fenofibric acid, an active metabolite...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)02109-5
更新日期:2003-08-15 00:00:00
abstract::The anti-migraine drug, eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1 H-indole; UK-116,044], is a novel 5-HT(1B/1D) receptor agonist. In this paper, the regional vasoconstrictor profile of eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibit...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00240-5
更新日期:2000-06-09 00:00:00
abstract::Elevated fatty acid levels play a pathogenic role in the development of insulin resistance, associated with type 2 diabetes. Interventions with ability to ameliorate fatty acid-induced insulin resistance might be useful for the management of diabetes. Here, we explored the effect of the diastereomeric mixture of calop...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.10.049
更新日期:2015-01-05 00:00:00
abstract::There has been a flurry of activity to develop agonists and antagonists for the member of the opioid receptor family, NOP receptor (also known as ORL1), in part to understand its role in pain. Modifications of a hexapeptide originally identified from a combinatorial library have led to the discovery of a high affinity...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.12.015
更新日期:2007-03-29 00:00:00
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::A high dose of apomorphine, a stimulator of brain dopamine receptors, caused a reduction in total sleep, intermediate sleep and a delayed appearance of paradoxical sleep. With a lower dose, a small and not significant trend toward an increase of paradoxical sleep was observed. Spiroperidol, considered as a specific bl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90340-x
更新日期:1976-08-01 00:00:00
abstract::Racemic baclofen, (-)-baclofen and muscimol depressed all spontaneously firing locus coeruleus neurons tested in a slice preparation. Racemic phaclofen (100 microM; 1 mM) moderately antagonized the effects of racemic baclofen without antagonizing those of muscimol. Bicuculline (10, 30, 100 microM) potently antagonized...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90061-1
更新日期:1988-04-27 00:00:00
abstract::Complete control of emesis caused by cyclophosphamide (CPA) is of immense interest to both patients and physicians. Serotonin 5-HT3- and tachykinin NK1-receptor antagonists are widely used antiemetics in clinic, but they fail to completely control CPA-induced emesis. New antiemetic targets for the full control of CPA-...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.09.080
更新日期:2014-01-05 00:00:00
abstract::Na+-H+ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We examined the potency of a novel Na+-H+ exchange inhibitor, SM-20550 [ N-(Aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and its effects on microv...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00283-6
更新日期:1999-06-25 00:00:00
abstract::alpha-Adrenoceptors have been classified into alpha(1)- and alpha(2)-adrenoceptors. Recently, the alpha(1)-adrenoceptors were divided into two subtypes: alpha(1L) with low affinity and alpha(1H) with high affinity for prazosin. Little is known concerning the role of each subtype of alpha(1)-adrenoceptor in asthma. We ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02248-3
更新日期:2002-09-27 00:00:00
abstract::Cholecystokinin (CCK) shows a potent influence on gastric secretion and motility but its role in gastric mucosal integrity has been little examined. In this study we found that exogenous CCK octapeptide protected gastric mucosa against ethanol-induced gastric injury but was ineffective against aspirin-induced damage. ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00674-v
更新日期:1995-01-24 00:00:00
abstract::Peroxynitrite, the reaction product of nitric oxide and superoxide, may contribute to vascular tissue oxidant stress in diabetes mellitus. The aim was to establish whether the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) could improve nitric oxide-depende...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.08.033
更新日期:2004-10-11 00:00:00
abstract::The present study investigates the role of cGMP and cAMP on the memory performance in the object recognition task in rats. The analogue 8-Br-GMP or 8-Br-cAMP was administered bilaterally into the hippocampus (0, 1, 3 and 10 microg in 0.5 microl saline/site) immediately after the exposure to two identical objects. Afte...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01614-4
更新日期:2002-02-01 00:00:00
abstract::It has been reported that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) can modulate opioid tolerance via its action on learning and memory. In this study, we examine if CaMKII can directly affect opioid tolerance. We found that spinal CaMKII activity was increased in rats tolerant to morphine. In these rats,...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01484-5
更新日期:2003-03-28 00:00:00
abstract::The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.06.013
更新日期:2013-08-15 00:00:00
abstract::Salidroside, an active constituent from the root of Rhodiola rosea L., has multiple pharmacological effects, such as anti-cancer, anti-inflammatory and anti-oxidative properties, etc. However, its protective effect on bone tissue via regulating calcium homeostasis is yet to be determined. This study was performed to i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.12.025
更新日期:2018-01-15 00:00:00
abstract::Histamine induced a dose-dependent stimulation of 3H-catecholamine(CA) efflux (superfusion procedure) from hypothalamic, striatal, hippocampal and cortical slices. The extra-hypothalamic regions were the most sensitive to histamine. Efflux of 14C-GABA and 14C-(acetyl)choline was not affected. The effect of histamine o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90126-1
更新日期:1977-05-15 00:00:00
abstract::Effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide (10.0-40.0 microg), on sleep and waking were studied in control, vehicle-treated and 6-hydroxydopamine-injected rats. Bilateral injections of m-chlorophenylbiguanide into the nucleus accumbens of the control and the vehicle-infused animals significantly in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00826-7
更新日期:1999-01-08 00:00:00
abstract::Age-related changes in pre- and postsynaptic alpha-adrenoceptors were investigated in prostatic and epididymal portions of vasa deferentia from young adult (2-3 month) and 24 month old Sprague-Dawley rats, using the selective alpha 1-agonist amidephrine and the selective alpha 2-agonist xylazine. Effects of agonists w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90631-3
更新日期:1983-11-25 00:00:00
abstract::(-)-Trans-epsilon-viniferin (epsilon-viniferin, 5-200 microM), a dimer of resveratrol, concentration-dependently inhibited the uptake of [3H]noradrenaline and [3H]5-HT by synaptosomes from rat brain (being slightly but significantly more selective against [3H]noradrenaline) and the uptake of [3H]5-HT by human platelet...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.06.005
更新日期:2006-08-07 00:00:00
abstract::Novel insulinotropic agent nateglinide stimulates insulin via binding to sulfonylurea receptor and closing the ATP-dependent K+ (K(ATP)) channels in pancreatic beta-cells, leading to an increase in [Ca(2+)](i) for exocytosis. The voltage-dependent Ca(2+) channel and the delayed rectifier K+ (Kv) channels are also pres...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01252-3
更新日期:2001-09-14 00:00:00
abstract::We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together wi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90264-5
更新日期:1992-01-28 00:00:00
abstract::The involvement of 5-HT receptors in the antinociceptive effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]py razole, was investigated in mice by means of the tail-pinch test. The antinociceptive effect of FR140423 injected i.t. was completely abolished by co-administration of the ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00832-3
更新日期:2000-12-08 00:00:00