Abstract:
:The protective potency of ischemic preconditioning decreases with increasing age. A key step in ischemic preconditioning is the opening of mitochondrial Ca(2+) sensitive K(+) (mK(Ca)) channels, which causes mild uncoupling of mitochondrial respiration. We hypothesized that aging reduces the effects of mK(Ca) channel opening on mitochondrial respiration. We measured the effects of mK(Ca) channel opener NS1619 (30 microM) on mitochondrial respiration in isolated heart mitochondria from young (2-3 months) and old (22-26 months) Wistar rats. Oxygen consumption was monitored online after addition of 250 microM ADP (state 3 respiration), and after complete phosphorylation of ADP to ATP (state 4 respiration) in the presence or absence of the mK(Ca) channel blocker paxilline (5 microM). The respiratory control index (RCI) was calculated as state 3/state 4. In mitochondria from young rats, NS1619 increased state 4 respiration by 11.9+/-4.1% (mean+/-S.E.M.), decreased state 3 respiration by 7.6+/-2.5%, and reduced the RCI from 2.6+/-0.03 (control) to 2.1+/-0.06 (all P<0.05, n=12 for all groups). Paxilline blocked the effect of NS1619 on state 4 respiration (0.7+/-2.8%), but did not affect the decrease in state 3 respiration; paxilline blunted the decrease of RCI. In mitochondria from old rats, NS1619 had neither effect on state 4 (0.4+/-1.6%), and state 3 respiration (-7.4+/-1.5%), nor on RCI (3.0+/-0.13 vs. 3.2+/-0.11, n=12). Increasing age reduced the effects of mK(Ca) opening on mitochondrial respiration. This might be one underlying reason of the decreased protective potency of ischemic preconditioning in the aged myocardium.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Heinen A,Winning A,Schlack W,Hollmann MW,Preckel B,Frässdorf J,Weber NCdoi
10.1016/j.ejphar.2007.09.008subject
Has Abstractpub_date
2008-01-14 00:00:00pages
108-13issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(07)01030-8journal_volume
578pub_type
杂志文章abstract::The effects of (S)-nafenodone, a new antidepressant, were studied on contraction and 45Ca2+ fluxes in rat vascular smooth muscle. In isolated rat aorta (S)-nafenodone, 10(-7) - 10(-4) M, inhibited the contractions induced by 80 mM KCl (IC50 = 1.4 +/- 0.4 x 10(-5) M) and 10(-5) M noradrenaline (IC50 = 1.2 +/- 0.2 x 10(...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90734-y
更新日期:1993-02-23 00:00:00
abstract::The functional role of metabotropic glutamate (mGlu) receptors in the rat dentate gyrus was investigated. By using extracellular recording techniques in slices, it was found that the depression induced by the mGlu receptor agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) was mediated through the mGlu grou...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00560-9
更新日期:1995-12-29 00:00:00
abstract::The present study aims to investigate whether azithromycin reverses P-glycoprotein-dependent anticancer drug resistance in vitro and modifies the hepatobiliary excretion of doxorubicin, a substrate for P-glycoprotein in vivo. Azithromycin increased dose-dependently the intracellular accumulation of doxorubicin in adri...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.11.035
更新日期:2004-01-26 00:00:00
abstract::Goniothalamin, a natural occurring styryl-lactone, is a novel compound with putative anticancer activities. In the present study, the mechanism of action of goniothalamin was further investigated in human breast cancer MDA-MB-231 cells. Goniothalamin treatment of cells significantly induced cell cycle arrest at G(2)/M...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.08.047
更新日期:2005-10-17 00:00:00
abstract::Ischemia-reperfusion injury(IRI), described as tissue damage caused by reversible ischemic injury or hypoxia prior to the blood supply restoration, is a common pathological phenomenon. In recent study, a hypoxia-reoxygenation (H/R) in the presence or absence of propofol posthypoxia treatment (P-PostH) cell model was b...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.05.039
更新日期:2018-08-15 00:00:00
abstract::Procaine and procainamide were covalently bound to acryloyl monomers and polymers. The dose-response and time-action parameters of the cardiac antiarrhythmic protection afforded by the prototype drugs and their acryloyl derivatives against chloroform-hypoxia-induced cardiac arrhythmias in unanesthetized mice and epine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90367-x
更新日期:1985-08-27 00:00:00
abstract::The study compared the efficacy of acute versus chronic metrifonate treatment to improve initial and reversal learning of the water maze spatial navigation task in medial septal-lesioned rats. Acute oral administration of 30 mg/kg metrifonate at 30 min, but not at 150 or 360 min, before training improved the initial a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)81936-x
更新日期:1997-11-05 00:00:00
abstract::The involvement of essential sulfhydryl groups in alpha 2-adrenoceptor function was investigated in the cerebral cortex of 7 and 70 day old rats. N-Ethylmaleimide (NEM) inhibited specific [3H]clonidine binding to cerebral cortical membranes in a concentration-dependent and biphasic manner in both infant and adult rats...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90169-3
更新日期:1983-08-05 00:00:00
abstract::Leukotriene C4 binding to mouse brain membranes was readily displaced by S-alkylglutathione derivatives, with the affinity of the test compound increasing as the alkyl chain length increases. S-decylglutathione was as potent as leukotriene C4. These data suggest that brain membrane leukotriene C4 binding sites are S-a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90186-6
更新日期:1989-02-14 00:00:00
abstract::The purpose of the present study was to investigate the effects of reactive oxygen species on the activity of epithelium-derived relaxant factor (EpDRF) released by guinea-pig tracheal epithelium. Reactive oxygen species were generated by the electrolysis of the physiological buffer in which the tissues were bathed. E...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00390-8
更新日期:1999-07-28 00:00:00
abstract::In order to identify new atypical antipsychotic drugs which are more selective for the human dopamine D4 receptor than for the human dopamine D2 (long) receptor, we tested enantiomer pairs of dopamine agonists and dopamine antagonists on the expressed proteins of these cloned receptors. The (+)-aporphines ((+)-N-propy...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90365-o
更新日期:1993-03-16 00:00:00
abstract::The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca2+) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.12.022
更新日期:2017-02-05 00:00:00
abstract::The effects of MCI-154, a cardiotonic agent which has direct effects on cardiac myofilaments, on postischemic contractile dysfunction were studied in dog heart subjected to a 30-min occlusion of the left anterior descending coronary artery followed by reperfusion, and compared with the effects of milrinone and dobutam...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90053-s
更新日期:1991-01-10 00:00:00
abstract::The anti-cancer effects of dioscin have been widely reported. However, its effect on laryngeal cancer remains unknown. In the present paper, our results showed that dioscin markedly caused cell apoptosis and DNA damage, increased reactive oxygen species (ROS) level, induced S-phase arrest, and inhibited invasion of hu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.02.009
更新日期:2016-03-05 00:00:00
abstract::The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate) , a thromboxane A2 synthase inhibitor, on eosinophil accumulation and activation were investigated in an experimental asthmatic guinea pig model and several cellular models. In the in vivo studies, CS-518 inhibited the bip...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90989-u
更新日期:1993-08-03 00:00:00
abstract::Alzheimer's disease is associated with glial activation and increased levels of the cytokines as well as impaired forebrain cholinergic function. Current therapies focus on enhancing cholinergic function by administrating acetylcholinesterase inhibitors, such as galantamine. Epidemiological results also suggest that a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02387-7
更新日期:2002-10-25 00:00:00
abstract::Rats were injected with 15 mg/kg (i.p.) mianserin or vehicle (saline) for 4, 10 or 21 days and 5-HT2 receptor binding and mRNA levels measured. Treatment with mianserin induced a substantial decrease in 5-HT2 radioligand binding (44-59% decrease; P less than 0.05 vs. control). No changes in the amount of 5-HT2 or, as ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(91)90093-w
更新日期:1991-06-19 00:00:00
abstract::Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zw...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.05.024
更新日期:2017-08-15 00:00:00
abstract::The pressor effect of 4-aminopyridine (4-AP) was studied in anesthetized cats and in isolated cat aortic ring preparations. A significant increase in blood pressure (38.9 +/- 11.4 mmHg) was observed following intravenous administration of 4-AP (0.3 mg/kg). The elevated blood pressure lasted for 1.3 h and returned to t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90343-7
更新日期:1985-07-11 00:00:00
abstract::This study addressed the possibility that acetylcholine-induced relaxation in the rabbit aorta is mediated by dual mechanisms: one N omega-nitro-L-arginine (NLA)-sensitive, the other glybenclamide-sensitive. Acetylcholine, nitroglycerin and BRL38227 (lemakalim), an activator of glybenclamide-sensitive potassium channe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90964-j
更新日期:1993-04-06 00:00:00
abstract::Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.04.030
更新日期:2012-06-15 00:00:00
abstract::Isolated porcine myocardial trabeculae from right atria and left ventricles were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Alpha calcitonin gene-related peptide (alpha-CGRP) increased contractile force in nearly half of the trabeculae, whereas th...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00721-9
更新日期:1999-12-03 00:00:00
abstract::Socially reared and isolation-reared rats treated chronically since weaning with alpha-flupenthixol showed elevated levels of spontaneous locomotor activity compared with control treated rats. However, chronic apomorphine treatment had no effect on spontaneous locomotor activity. Chronic alpha-flupenthixol treatment e...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90019-4
更新日期:1976-05-01 00:00:00
abstract::The (+)-enantiomer of the dihydropyridine 202-791 produced coronary constrictor and positive inotropic effects in Langendorff-perfused rat hearts whereas (--)-202-791 showed coronary dilator and negative inotropic effects. Both enantiomers showed the vascular effects at lower concentrations than the myocardial effects...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90723-5
更新日期:1986-04-29 00:00:00
abstract::Toluene diisocyanate (TDI)-induced asthma is a frequent occupational airway disease. To determine whether a calibrated dosage of oral slow-release theophylline inhibits asthmatic reactions and the associated increase of airway responsiveness to methacholine induced by TDI, we examined six asthmatic subjects who develo...
journal_title:European journal of pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0926-6917(92)90010-a
更新日期:1992-05-01 00:00:00
abstract::The effect of lithium ion (Li+) on receptor-mediated synthesis of cyclic GMP, a putative second messenger, was examined using intact murine neuroblastoma cells (clone N1E-115). Lithium chloride potently inhibited cyclic GMP formation stimulated by the neuropeptides, neurotensin, angiotensin II and bradykinin in an ide...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90745-4
更新日期:1986-07-15 00:00:00
abstract::The antiparkinsonian agent l-deprenyl is metabolized to l-methamphetamine and l-amphetamine and, at higher doses, can facilitate the release and inhibit the reuptake of dopamine. Since l-deprenyl can affect dopamine release and reuptake it was important to evaluate it for cocaine-like discriminative stimulus effects. ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90650-5
更新日期:1994-07-11 00:00:00
abstract::Clinically, dexamethasone is known to reduce cerebral edema. To further investigate the mechanism of this neuroprotection, an in vitro model of brain-derived microvessel endothelial cells (BME cells) was used to investigate the effect of dexamethasone on hypoxia-induced hyperpermeability. Furthermore, the expression o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00915-8
更新日期:2001-01-12 00:00:00
abstract::Scopolamine, a non-selective muscarinic receptor antagonist has widespread central nervous system effects. Muscarinic receptors located in the central nervous system play a vital role in the modulation of impulsivity. The objective of the current study was to evaluate the effect of scopolamine on impulsivity using dif...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.10.005
更新日期:2013-11-15 00:00:00
abstract::Selective serotonin reuptake inhibitors (SSRIs) are known to cause sexual dysfunction, such as decreased sexual motivation, desire, arousal, and orgasm difficulties. These SSRI-induced sexual complaints have a high prevalence rate, while there is no approved pharmacological treatment for SSRI-induced sexual dysfunctio...
journal_title:European journal of pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ejphar.2014.10.061
更新日期:2015-04-15 00:00:00