Abstract:
:Accumulating evidence indicates protective actions of mineralocorticoid antagonists (MR antagonists) on cardiovascular pathology, which includes blunting vascular inflammation and myocardial fibrosis. We examined the anti-inflammatory and anti-fibrotic potential of MR antagonists in rodent respiratory models. In an ovalbumin allergic and challenged Brown Norway rat model, the total cell count in nasal lavage was 29,348 ± 5451, which was blocked by spironolactone (0.3-60 mg/kg, p.o.) and eplerenone (0.3-30 mg/kg, p.o.). We also found that MR antagonists attenuated pulmonary inflammation in the Brown Norway rat. A series of experiments were conducted to determine the actions of MR blockade in acute/chronic lung injury models. (1) Ex vivo lung slice rat experiments found that eplerenone (0.01 and 10 µM) and spironolactone (10 µM) diminished lung hydroxyproline concentrations by 55 ± 5, 122 ± 9, and 83 ± 8%. (2) In in vivo studies, MR antagonists attenuated the increases in bronchioalveolar lavage (BAL) neutrophils and macrophages caused by lung bleomycin exposure. In separate studies, bleomycin (4.0 U/kg, i.t.) increased lung levels of hydroxyproline by approximately 155%, which was blocked by spironolactone (10-60 mg/kg, p.o.). In a rat Lipopolysaccharide (LPS) model, spironolactone inhibited acute increases in BAL cytokines with moderate effects on neutrophils. Finally, we found that chronic LPS exposure significantly increased end expiratory lung and decreased lung elastance in the mouse. These functional effects of chronic LPS were improved by MR antagonists. Our results demonstrate that MR antagonists have significant pharmacological actions in the respiratory system.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lieber GB,Fernandez X,Mingo GG,Jia Y,Caniga M,Gil MA,Keshwani S,Woodhouse JD,Cicmil M,Moy LY,Kelly N,Jimenez J,Crawley Y,Anthes JC,Klappenbach J,Ma YL,McLeod RLdoi
10.1016/j.ejphar.2013.08.019subject
Has Abstractpub_date
2013-10-15 00:00:00pages
290-8issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(13)00609-2journal_volume
718pub_type
杂志文章abstract::Bupropion is a weakly potent central nervous system (CNS) stimulant that is marketed both as an antidepressant and as an anti-smoking aid. The mechanism(s) by which it produces its effects is not well understood. In the present study, the effect of bupropion was examined in rats trained to discriminate the stimulus ef...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01554-6
更新日期:2002-05-17 00:00:00
abstract::The presence of neuronal nicotinic acetylcholine receptors in rabbit corpus cavernosum tissue and possible mechanisms underlying the potentiation of electrical field stimulation induced relaxation by nicotine were analyzed. In corpus cavernosum tissue strips nicotine (3 x 10(-5) M) and acetylcholine (10(-3) M) produce...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.11.053
更新日期:2007-03-08 00:00:00
abstract::The relationship between isometric tension and the increase in cyclic GMP level associated with the initial phase of drug-induced contraction of taenia coli was studied. Maximal contraction induced by 100 micrometers carbachol or 124 mM KCl occurred in 30 sec and was associated with an increase in cyclic GMP levels of...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90209-0
更新日期:1981-03-12 00:00:00
abstract::Translational research for neurodegenerative disease depends intimately upon animal models. Unfortunately, promising therapies developed using mouse models mostly fail in clinical trials, highlighting uncertainty about how well mouse models mimic human neurodegenerative disease at the molecular level. We compared the ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2015.03.021
更新日期:2015-07-15 00:00:00
abstract::Aripiprazole is the first dopamine D(2)/D(3) receptor partial agonist approved for use in the treatment of psychiatric disorders including schizophrenia, bipolar disorder, and unipolar depression in the US. Aripiprazole has demonstrated a relatively favorable side effect profile compared to other commonly prescribed a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.02.007
更新日期:2009-04-01 00:00:00
abstract::The activation of adenosine A(2B) receptors in human mast cells causes pro-inflammatory responses such as the secretion of interleukin-8. There is evidence for an inhibitory effect of benzodiazepines on mast cell mediated symptoms in patients with systemic mast cell activation disease. Therefore, we investigated the e...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.12.003
更新日期:2013-01-30 00:00:00
abstract::In the guinea-pig isolated ileum, beta-(2-thienyl)-gamma-aminobutyric acid (BTG; 100-500 microM) reversibly and competitively (pA2 = 4.3 +/- 0.1) antagonised the baclofen-induced (5-100 microM) depression of cholinergic twitch contractions, but not that to adenosine or morphine. By contrast, in rat neocortical slice p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90784-2
更新日期:1992-10-06 00:00:00
abstract::Two splice variants of the pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PACAP receptor and PACAP/HOP receptor isoform) were stably expressed in Chinese hamster ovary (CHO) cells that did not express constitutively receptors for this family of peptides. The PACAP/HOP receptor protein had ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(95)90037-3
更新日期:1995-02-15 00:00:00
abstract::RES-701-1 (cyclic (Gly1-Asp9)(Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe- Phe-Asn-Tyr-Tyr-Trp)), a peptide isolated from Streptomyces sp., has been reported to inhibit the endothelin ETB receptor. We examined the effects of this peptide on the blood vessels and the small intestine. In isolated rat aorta without endot...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90739-0
更新日期:1994-09-12 00:00:00
abstract::Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare monogenic idiopathic partial epilepsy characterized by clusters of frontal lobe motor seizures during sleep. Recently, it has been shown that mutations of the chromosome-20q-located neuronal nicotinic acetylcholine receptor alpha4-subunit (CHRNA4) a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00065-0
更新日期:2000-03-30 00:00:00
abstract::The effect of (+)-sotalol and deoxysotalol on prostaglandin (PGF2a and 15-methyl PGF2alpha)-evoked contractions was studied using the isolated rat uterus. After control responses to prostaglandins had been obtained the uterus was exposed to the nutrient fluid containing 10 microgram/ml of (+)-sotalol, deoxysotalol or ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90138-8
更新日期:1977-11-01 00:00:00
abstract::A 5-min period of cerebral ischemia induced in rats by the four-vessel occlusion method increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by a working memory procedure applied in a three-panel runway task. The protein kinase C (PKC) i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90844-g
更新日期:1991-10-29 00:00:00
abstract::Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (dbcAMP) at varying concentrations as low as 1 X 10(-4)M. A positive inotropic effect was observed with all concentrations of dbcAMP. Concomitant administration of 5 X 10(-4)M monobutyryl guanosine 3',5'-monophosphat...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90280-6
更新日期:1976-03-01 00:00:00
abstract::Di-isobutyryl apomorphine (5 mg/kg i.p.) and lergotrile (5 mg/kg i.p.) produce long lasting turning behaviour in rats with 6-hydroxydopamine lesions at the level of the substantia nigra. Haloperidol (1.5 and 3.0 mg/kg p.o.) blocks the rotational behaviour due to the apomorphine ester but has no effect on lergotrile tu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90063-2
更新日期:1977-09-01 00:00:00
abstract::Due to the limited results achieved in the clinical treatment of heart failure, a new inotropic strategy of myosin motor activation has been developed. The lead molecule of myosin activator agents is omecamtiv mecarbil, which binds directly to the heavy chain of the cardiac β-myosin and enhances cardiac contractility ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.05.027
更新日期:2017-08-15 00:00:00
abstract::This report describes the molecular pharmacological properties of LR-B/081 (methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5- yl) [1,1'-biphenyl]-4-yl]methyl]-1 (6H)-pyrimidinyl]methyl]- 3-thiophenecarboxilate), a novel non-peptide angiotensin II receptor antagonist. This compound potently displaced [3H]angiote...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(95)90028-4
更新日期:1995-07-18 00:00:00
abstract::A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its alpha-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24-100% range. However, phentolamine produced 100% relaxation w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90534-b
更新日期:1992-02-11 00:00:00
abstract::In view of the scarce information about the analgesic mechanism of kappa-opioid receptor agonists, the objective of the present study was to determine whether nitric oxide (NO) is involved in the peripheral antinociception of bremazocine, a kappa-opioid receptor agonist. Three drugs all interfering with the L-arginine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02275-6
更新日期:2002-11-01 00:00:00
abstract::The in vivo and in vitro effects of melatonin on enzyme activity of glutathione reductase (Glutathione: NADP(+) oxidoreductase, EC 1.8.1.7; GR) were investigated in this study. Glutathione reductase was purified from human erythrocytes 5.823-fold with a yield of 24% by ammonium sulfate fractionation, affinity chromato...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.03.040
更新日期:2006-05-10 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::Local anesthetics bind to dopamine transporters and inhibit dopamine uptake in rodent brain. Additionally, local anesthetics are self-administered in rhesus monkeys. The present study determined binding affinities of cocaine and five local anesthetics at dopamine transporters in rhesus monkey brain, and compared bindi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00967-4
更新日期:1999-02-19 00:00:00
abstract::The anti-inflammatory activity of avarol and avarone, sesquiterpenoid derivatives from the Mediterranean sponge Dysidea avara, was investigated. Both compounds potently inhibited paw oedema induced by carrageenan (approximated ED50 = 9.2 and 4.6 mg/kg, p.o., respectively) as well as ear oedema induced by 12-O-tetradec...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90759-5
更新日期:1994-02-21 00:00:00
abstract::The effect of selective D1 receptor agonists on acetylcholine (ACh) release in the striatum was investigated using in vivo microdialysis. Administration of the reactive enantiomer, (+)-SKF 38393 (2, 10 mg/kg s.c.), doses which elevate grooming and sniffing behaviour, increased ACh release by 40 and 75%, respectively. ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90456-g
更新日期:1990-09-21 00:00:00
abstract::Pregnant rats were infused with phentermine plus dexfenfluramine from days 3 through 17 of gestation. Control rats were either pair-fed or were fed ad libitum. There were no effects of prenatal drug treatment on number of offspring, their birth weights, or on their motor coordination assessed at 11 days of age. Mother...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00100-4
更新日期:1999-03-26 00:00:00
abstract::This study evaluated the possible involvement of 5-HT(2B) receptors in long-lasting hypotension to 5-hydroxytryptamine (5-HT), which is predominantly mediated by 5-HT7 receptors, in anaesthetised vagosympathectomized rats. Intravenous injections of 5-HT and 5-carboxamidotryptamine (5-CT) elicited a dose-dependent hypo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.08.050
更新日期:2004-10-19 00:00:00
abstract::Prazosin is believed to have an antihypertensive action due to a selective blockade of alpha-adrenoceptors on vascular smooth muscle. Using an in vitro autoradiographic technique specific binding of [3H]prazosin to the abdominal aorta and renal artery in the rat has been shown. The binding of [3H]prazosin to arterial ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90380-6
更新日期:1982-02-19 00:00:00
abstract::Flavonoids are polyphenols frequently consumed in the diet they have been suggested to exert a number of beneficial actions on human health, including anti-inflammatory activity. This study investigated the immunomodulatory effects of two flavonoids, Chrysin and Hesperetin. The effects of flavonoids on B and T cell pr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.07.017
更新日期:2017-10-05 00:00:00
abstract::Vasoconstrictor responses elicited by periarterial electrical nerve stimulation were analyzed pharmacologically in the canine isolated, perfused intermediate auricular artery. Phentolamine (10 microM) significantly inhibited the vasoconstrictor responses to stimulation at 5 Hz and over but not those to stimulation at ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01121-7
更新日期:1997-08-27 00:00:00
abstract::FR134043, disodium(Z,1S,15S,8S,24S,27R,29S,34S,37R)-29-ben zyl-21-ethylidene-27-hydroxy-15-isobutyrylamino-34-isopropyl-31,37 -dimethyl-10,16,19,22,30,32,35,38-octaoxo-36-oxa-9,11,17,20,23,28, 31,33-octaazatetracyclo[16.13.6.1(24),(28).0(3),(8)]octatricont a-3,5,7-trien-5,6-diyl disulfate, is a water-soluble inhibitor...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00028-4
更新日期:1998-03-26 00:00:00
abstract::Many studies have demonstrated that cyclophosphamide (CPA) can affect hepatic cytochrome p450 (CYP) isoenzyme activity in animals. We have investigated the effect of CPA on gene expression of various CYP enzymes as well as beta-actin in the human acute promyelocytic leukemia cell line (HL-60S) and its multidrug-resist...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01995-7
更新日期:2002-08-09 00:00:00