Abstract：
:Inhibitors of Na(+)/H(+) exchanger (NHE) 1 have been shown to exert protective effects on various myocardial injuries. In this study, we characterized the pharmacodynamic properties of new guanidine NHE1 inhibitors (cariporide, sabiporide, KR-32511, KR-32570, and KR-33028) to analyze their myocardial protective effects. Although NHE1 is the major NHE isoform in cardiomyocytes, IC(50)values of these chemicals tested in rat cardiomyocytes were significantly different from those in PS120/hNHE1 cells where human NHE1 is heterologously expressed. In rat cardiomyocytes, KR-32570 and KR-33028 exhibited the highest potencies and their IC(50)values were 7+/-2 nM and 9+/-3 nM, respectively. The IC(50)values of all the chemicals tested on rat submandibular gland NHE2 were in the micromolar range, and they showed no inhibitory effects on hNHE3 and epithelial Na(+) channels up to 30 microM, suggesting a high selectivity toward NHE1. Sabiporide and KR-32570 exhibited slow dissociation kinetics with NHE1 inhibition persisting even after rinsing-out. When the cytoprotective effects of chemicals against hypoxic damage of rat cardiomyocytes were examined, the order of potency was KR-32570>or=KR-33028>sabiporide>cariporide>KR-32511. This order was exactly the same as that for the NHE1 inhibition in rat cardiomyocytes and did not correlate with any other properties, including the slow dissociation kinetics. Taken together, these results suggest that KR-32570 and KR-33028 are potent candidates for cardioprotective agents, and that the IC(50) in the target organ is the most critical factor governing the cytoprotective effects of NHE1 inhibitors.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Kim J,Jung YS,Han W,Kim MY,Namkung W,Lee BH,Yi KY,Yoo SE,Lee MG,Kim KHdoi
10.1016/j.ejphar.2007.03.056subject
Has Abstractpub_date
2007-07-12 00:00:00pages
131-8issue
1-2eissn
0014-2999issn
1879-0712pii
S0014-2999(07)00440-2journal_volume
567pub_type
杂志文章abstract：:Cardiovascular and behavioral responses induced by intravenous administration of the serotonin (5-HT)1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in conscious normotensive rats either after a single administration, after repeated subcutaneous treatments (1 mg/kg daily for 3 day...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90140-l
更新日期：1991-02-14 00:00:00
abstract：:We examined whether the proteinase-activated receptor-2 (PAR2) agonist, H-Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL-NH2), could induce scratching behavior in mice. Intradermal injections of SLIGRL-NH2 (10-50 microg) evoked dose dependent scratching. This behavior peaked near 5 min and returned to preinjection levels within ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.11.012
更新日期：2006-01-20 00:00:00
abstract：:To investigate the mechanism underlying sulpiride-induced catalepsy, we simultaneously examined cataleptic behavior and the kinetics of the dopamine receptor antagonist, sulpiride of dopamine, and the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), using in vivo voltammetry. After intrastriatal administrat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)00140-4
更新日期：1997-05-12 00:00:00
abstract：:The involvement of tachykinin NK1 receptors in the plasma protein extravasation (measured by the Evans blue leakage technique) produced by intravenous administration of capsaicin was investigated in the urinary bladder and trachea of anesthetized rats. Capsaicin-induced plasma extravasation was markedly inhibited by (...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90183-q
更新日期：1991-12-17 00:00:00
abstract：:The kappa-opioid receptor (kappa Op) from guinea-pig cerebellum membranes has been solubilized in an active form and in good yield (30-40%) with digitonin in 10 mM Tes-KOH buffer, pH 7.4. [3H]Bremazocine (KD = 1.1 nM in the soluble extract) was used to monitor the binding and hydrodynamic characteristics of the digito...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90755-8
更新日期：1988-05-20 00:00:00
abstract：:Recombinant human GABA(A) receptors were investigated in vitro by coexpression of cDNAs coding for alpha1, beta2, and gamma2 subunits in the baculovirus/Sf-9 insect cell system. We report that a single amino acid exchange (isoleucine 121 to valine 121) in the N-terminal, extracellular part of the alpha1 subunit induce...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1997-06-25 00:00:00
abstract：:Neither the chronic administration (40 daily subcutaneous injections) of nicotine (0.4 mg/kg) nor its withdrawal (3 days) influenced avoidance of the more aversive open runways of an elevated X-maze in rats which had been habituated to the apparatus. Lesions of the serotonergic fibres innervating the hippocampus incre...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90278-0
更新日期：1987-09-11 00:00:00
abstract：:Unilateral ureteral obstruction (UUO) is a well-established method to study interstitial fibrosis of the kidney. In this study, we investigated the effects of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed kidne...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.03.041
更新日期：2016-06-05 00:00:00
abstract：:In this work, the involvement of ionotropic glutamatergic receptors and nitric oxide on striatal dopamine release induced by anatoxin-a was investigated in conscious and freely-moving rats. To study the participation of glutamatergic receptors, the effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (A...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.07.044
更新日期：2006-10-24 00:00:00
abstract：:The present study was aimed to evaluate the antihypertensive effect of diosmin in deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA (25 mg/kg body weight) and 1% NaCl in the drinking water ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.12.040
更新日期：2012-03-15 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 bronchial smooth muscle of the rat was examined for contractile responses to excitatory amino acids. The nerve-mediated contraction induced by electrical field stimulation was enhanced by exogenous L-glutamate (L-Glu). The apparent affinity (ED50) of L-Glu was 3.5 +/- 0.1 mM. Both tetrodotoxin and hemicholinium-3 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90235-5
更新日期：1989-05-02 00:00:00
abstract：:Pyrrolidine dithiocarbamate (PDTC) can form a complex with metal ions and then act as a proteasome inhibitor, which leads to tumor cell apoptosis, and could therefore be developed as an anticancer agent. In our efforts to find factors that induce PDTC-mediated apoptosis of tumor cells, the effect of serum concentratio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.09.048
更新日期：2010-12-15 00:00:00
abstract：:Local administration of amitriptyline into the rat hindpaw produces peripheral antinociception; this is reduced by adenosine receptor antagonists and appears to involve endogenous adenosine. The present study used peripheral microdialysis: (a) to determine whether amitriptyline could enhance extracellular tissue level...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.06.030
更新日期：2005-08-22 00:00:00
abstract：:Neuromedin K, a decapeptide isolated from porcine spinal cord and suggested to have tachykinin-like activity in vitro, produced reciprocal hind-limb scratching when injected intrathecally to mice. Neuromedin K was 20-60 times less potent in producing scratching (on a molar basis) than substance P, kassinin, eledoisin ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90499-0
更新日期：1984-08-17 00:00:00
abstract：:The purposes of the present study were to clarify whether some Cl(-) channels exist in rat pleural mesothelial cells, and to investigate functional and molecular characteristics of these channels. Electrophysiological recordings were performed at room temperature using the whole-cell configuration of the patch-clamp t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.05.001
更新日期：2009-07-01 00:00:00
abstract：:Single myocytes isolated from the guinea-pig ventricle were used under voltage-clamp conditions to study the activity of a newly developed drug, R56865, a benzothiazolamine derivative, against digitalis toxicity. Multicellular Purkinje preparations were used in some experiments. The drug blocked the transient inward c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90407-h
更新日期：1991-04-10 00:00:00
abstract：:The steady-state levels and utilization (alpha-MPT-induced disappearance) of noradrenaline (NA) and dopamine (DA) were measured in distinct mouse brain nuclei after acute morphine challenge, in mice rendered tolerant to morphine, and during the naloxone-precipitated morphine withdrawal syndrome. Mouse brain nuclei con...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90132-2
更新日期：1983-09-30 00:00:00
abstract：:Recent studies in this laboratory have demonstrated the ability of acetylcholine receptor agonists to produce systemic arterial pressor responses through stimulation of spinal muscarinic receptors. In urethane-anesthetized rats a new surgical procedure was employed to permit microinjection of drugs into the cerebrospi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90039-k
更新日期：1993-12-21 00:00:00
abstract：:Endothelial cells from rat brain microvessels, human aortic artery and human umbilical vein were examined, together with ex vivo rat brain capillaries and rat aortic ring sections, for the expression of opioid receptor-like OP-4 mRNA and protein. High levels of mRNA expression and an immunopositive reaction for the re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.09.049
更新日期：2003-12-15 00:00:00
abstract：:Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and µ-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU0...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.09.021
更新日期：2015-10-15 00:00:00
abstract：:The effects of some alpha 1-adrenoceptor antagonists (prazosin, nonselective for the alpha 1A- and alpha 1B-adrenoceptor subtypes; 5-methyl-urapidil, selective for the alpha 1A-adrenoceptor subtype; chloroethylclonidine, selective for the alpha 1B-adrenoceptor subtype) and nifedipine were compared on contractile respo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90223-2
更新日期：1994-11-14 00:00:00
abstract：:Compared with sham-operated guinea pigs, chronic heart failure produced by aortic constriction resulted in a 79% increase in alpha 1-adrenoceptor density as measured by [3H]prazosin binding (73 +/- 15 vs. 131 +/- 20 fmol/mg protein, P < 0.05); beta-adrenoceptor number, measured by (-)-[3H]dihydroalprenolol binding, in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90017-5
更新日期：1980-10-03 00:00:00
abstract：:UP 269-6, 5-methyl-7-propyl-8(-)[2'-(1H-tetrazol-5-yl)biphenyl-4- yl)methyl]-1,2,4-triazolo]1,5-c]pyrimidin-2(3H)-one is a novel nonpeptide angiotensin II receptor antagonist. In vivo studies were performed to evaluate UP 269-6 for its angiotensin II antagonistic action. In pithed rats, i.v. administration of UP 269-6...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00395-2
更新日期：1995-09-15 00:00:00
abstract：:Drugs of abuse and stress are associated with changes in circulating cell populations and reductions in cell-mediated immune responses. The main goal of this study was to determine the influence of repeated and acute d-amphetamine treatments on the foot-shock stress-induced effects on the peripheral lymphocyte subpopu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.02.007
更新日期：2008-04-28 00:00:00
abstract：:The effects of mixed dietary coenzyme Q(9), alpha-tocopherol, and beta-carotene on immune cell activity and blood cytokine profile were studied in peritoneal macrophages, spleen lymphocytes, and blood plasma from mice with acute inflammation induced by lipopolysaccharide (LPS). The activity of each fat-soluble antioxi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.05.004
更新日期：2009-08-01 00:00:00
abstract：:The effect of NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) on late-phase airway responses and airway hyperreactivity was investigated in the guinea pig. Challenge with inhaled ovalbumin in conscious guinea pigs actively sensitized with inhaled ovalbumin caused triphasic bronchial obstruction, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90490-h
更新日期：1991-07-09 00:00:00
abstract：:Opioid agonists and antagonists can regulate the density of mu-opioid receptors in whole animal and in cell culture. High intrinsic efficacy agonists (e.g., etorphine), but not lower intrinsic efficacy agonists (e.g., morphine), produce mu-opioid receptor down-regulation and can alter the abundance of mu-opioid recept...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.07.052
更新日期：2004-09-13 00:00:00
abstract：:The present study was undertaken to compare the properties of the [3H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) binding site in the dorsal raphe nucleus with the hippocampal 5-HT1A receptor. In both tissues inclusion of 1 mM Mg2+ enhanced specific [3H]8-OH-DPAT binding, while 1 mM GTP decreased radioligand bi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)10113-3
更新日期：1997-06-18 00:00:00
abstract：:The aim of the present study was to determine the effect of a calcium channel blocker on renal function, urinary endothelin excretion and endothelin receptor number in rats. Administration of cyclosporine resulted in a significant impairment of renal function when measured by either [14C]inulin or 24 h creatinine clea...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90132-a
更新日期：1991-02-26 00:00:00
