Abstract:
:This study was designed to determine whether K+ channels play a role in nitric oxide (NO)-dependent acetylcholine relaxation in porcine internal mammary artery (IMA). IMA segments were isolated and mounted in organ baths to record isometric tension. Acetylcholine-elicited vasodilation was abolished by muscarinic receptor blockade with atropine (10(-6)M). Incubation with indomethacin (3 x 10(-6)M), superoxide dismutase (150 U/ml) and bosentan (10(-5)M) did not modify the acetylcholine response ruling out the participation of cyclooxygenase-derivates, reactive oxygen species or endothelin. The relaxation response to acetylcholine was strongly diminished by NO synthase- or soluble guanylyl cyclase-inhibition using L-NOArg (10(-4)M) or ODQ (3 x 10(-6)M), respectively. The vasodilation induced by acetylcholine and a NO donor (NaNO(2)) was reduced when rings were contracted with an enriched K+ solution (30 mM), by voltage-dependent K+ (K(v)) channel blockade with 4-amynopiridine (4-AP; 10(-4)M), by Ca(2+)-activated K+ (K(Ca)) channel blockade with tetraethylammonium (TEA; 10(-3)M), and by apamin (5 x 10(-7)M) plus charybdotoxin (ChTx; 10(-7)M) but not when these were added alone. In contrast, large conductance K(Ca) (BK(Ca)), ATP-sensitive K+ (K(ATP)) and inwardly rectifying K+ (K(ir)) channel blockade with iberiotoxin (IbTx; 10(-7)M), glibenclamide (10(-6)M) and BaCl(2) (3 x 10(-5)M), respectively, did not alter the concentration-response curves to acetylcholine and NaNO(2). Na+-K+ ATPase pump inhibition with ouabain (10(-5)M) practically abolished acetylcholine and NaNO(2) relaxations. Our findings suggest that acetylcholine-induced relaxation is largely mediated through the NO-cGMP pathway, involving apamin plus ChTx-sensitive K+ and K(v) channels, and Na+-K+-ATPase pump activation.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Pagán RM,Prieto D,Hernández M,Correa C,García-Sacristán A,Benedito S,Martínez ACdoi
10.1016/j.ejphar.2010.05.004subject
Has Abstractpub_date
2010-09-01 00:00:00pages
61-6issue
1eissn
0014-2999issn
1879-0712pii
S0014-2999(10)00420-6journal_volume
641pub_type
杂志文章abstract::We have investigated the effects of substituting extracellular Na+ by choline or K+ on responses of quin2- and fura-2-loaded human platelets to thrombin and platelet-activating factor (PAF). Na+ substitution by choline did not affect the extent of the rise in [Ca2+]i evoked by either agonist. The response to thrombin,...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90563-7
更新日期:1986-08-22 00:00:00
abstract::Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11)), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depol...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90612-7
更新日期:1988-08-24 00:00:00
abstract::Whether sulfonylurea therapy, which blocks ATP-sensitive K+ (KATP) channels, impedes endogenous cardioprotective mechanisms during cellular metabolic impairment remains controversial. Therefore, the effect of glyburide, a prototype sulphonylurea drug, on cytosolic Ca2+ concentration and KATP channel activity, was meas...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00327-5
更新日期:1996-07-25 00:00:00
abstract::The inward chloride current induced by angiotensin II (AII) in Xenopus oocytes shows strong and homologous desensitization, and was suggested to be mediated by phosphatidylinositol (PI) hydrolysis (Sakuta et al., 1991, Eur. J. Pharmacol. Mol. Pharmacol. 208, 31). As a model of agonist-induced desensitization of recept...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(91)90049-n
更新日期:1991-09-12 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::Bilateral injections of alpha-methylnoradrenaline into the area of the nucleus tractus solitarii of the brain stem caused a dose-dependent decrease of systemic arterial blood pressure and heart rate of anesthetized rats. The effects were prevented and even reversed by a preceding injection of the alpha-adrenoceptor bl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90305-2
更新日期:1975-06-01 00:00:00
abstract::Itching is known as a commonly side effect of opioid administration. However, the relationship of opioid receptors to itching is unclear. In this study, we examined the effect of intradermal injection of morphine and fentanyl on the itching sensation. When injected intradermally into the rostral back of mice, morphine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.10.066
更新日期:2010-02-10 00:00:00
abstract::Tricyclic antidepressants have analgesic and sedative effects in addition to their antidepressive properties. We tested the acute analgesic and locomotor inhibitory effects of the tricyclic antidepressant amitriptyline and the alpha(2)-adrenoceptor agonist clonidine in wild-type control and in alpha(2A)-adrenoceptor k...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.11.047
更新日期:2004-02-06 00:00:00
abstract::Selective serotonin reuptake inhibitors (SSRIs) are widely used as a first-line therapy in postpartum depression. The objective of this study was to determine the mechanism underlying the inhibitory effects of the SSRI, fluvoxamine, on β-casein expression, an indicator of lactation, in MCF-12A human mammary epithelial...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2015.09.038
更新日期:2015-11-05 00:00:00
abstract::Intraperitoneal administration of (--)-sulpiride (12 to 50 mg/kg) produced a dose-related decrease in cGMP content in cerebellar cortex, while the (+)-sulpiride (10 microgram), but not after intracerebellar injection. These findings support the contention that (--)-sulpiride modifies cerebellar cGMP levels through and...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90203-6
更新日期:1979-05-01 00:00:00
abstract::The influence of decreased endogenous gamma-aminobutyric acid (GABA) concentration on benzodiazepine receptor function was studied in the brain of living baboons. Positron emission tomography and the radiotracer [11C]flumazenil combined with electroencephalography were used to determine the pharmacological properties ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)00004-6
更新日期:1997-02-19 00:00:00
abstract::Angiotensin-converting enzymes, ACE and ACE2, are key members of renin angiotensin system. Activation of ACE2/Ang-(1-7) pathway enhances cardiovascular protective functions of bone marrow-derived stem/progenitor cells. The current study evaluated the selectivity of ACE2 inhibitors, MLN-4760 and DX-600, and ACE and ACE...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.01.007
更新日期:2016-03-05 00:00:00
abstract::Factor Xa inhibitors reduce stroke in patients with atrial fibrillation. Pulmonary veins (PVs) and the sinoatrial node (SAN) are crucial for genesis of atrial fibrillation. However, the electrophysiological effects of factor Xa inhibitors (edoxaban and rivaroxaban) on PVs and the SAN remain unclear. Conventional micro...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.07.003
更新日期:2018-08-15 00:00:00
abstract::Hydrolysis of ([3H]Leu5)-enkephalin into the tripeptide [3H]Tyr-Gly-Gly can be detected using particulate fractions from a variety of peripheral organs. In some tissues, e.g. exocrine and endocrine glands, this dipeptidyl carboxypeptidase ("enkephalinase") activity is even higher than in brain. ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90609-9
更新日期:1981-01-05 00:00:00
abstract::Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS beta-adrenoceptors and attenuate brain adenylate cyclase activity, beta-adrenoceptor agonists may also possess antidepressant properties. We compared the effects of the centrally acting beta-adrenocepto...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90158-0
更新日期:1987-02-10 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::Concentration-relaxation curves for pinacidil and cromakalim were obtained in isolated guinea-pig tracheas contracted by histamine. Pinacidil produced complete relaxation with an EC50 value of 2.8 microM. The antidiabetic sulfonylurea, glibenclamide (0.1, 1, 10 microM), caused concentration-dependent rightward shifts ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90312-t
更新日期:1990-05-16 00:00:00
abstract::Topical glucocorticoid treatment (betamethasone-17-valerate (0.018 mg/cm2, 3 h pretreatment) significantly inhibited neurogenic oedema formation induced by electrical antidromic stimulation (2 Hz, 15 V, 0.1 ms for 5 min) of the rat saphenous nerve; a response mediated by neuropeptides released from activated capsaicin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00350-t
更新日期:1995-09-05 00:00:00
abstract::The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor and is associated with angiotensin-(1-7) signaling. We investigated the effect of Mas-deficiency on blood pressure regulation under physiological conditions and salt load using radiotelemetry. Mas-knockout mice and t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.05.025
更新日期:2012-08-15 00:00:00
abstract::We designed a randomized controlled study to identify and compare the liver tissue responses in systemic hypoxia and resuscitation with 21% and 100% oxygen using an animal model of neonatal hypoxia and reoxygenation. Twenty-seven piglets (1-3 days old, weight 1.5-2.0 kg) were acutely instrumented and mechanically vent...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.11.019
更新日期:2008-02-12 00:00:00
abstract::The intracerebroventricularly (i.c.v.) injected presynaptic alpha2-adrenoceptor agonists, clonidine and oxymetazoline, exerted a dose-dependent inhibition on the gastric acid secretion in pylorus-ligated rats; the ED50 values were 20 and 7.5 nmol/rat, respectively. Moreover, beta-endorphin, given i.c.v., also decrease...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01572-2
更新日期:2002-01-25 00:00:00
abstract::The effect of three selective bradykinin B(2) receptor antagonists, MEN11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic-Arg)c(7gamma-1 0alpha)), Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH), and FR173567 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2, 4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]-N-me...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00882-1
更新日期:2000-01-28 00:00:00
abstract::Low levels of serotonin may reduce the density of the serotonin transporter (SERT) by either increasing trafficking or reducing synthesis; a "neuroadaptive response". To determine whether 3,4-methylenedioxymethamphetamine (MDMA)-induced reductions in SERT density could be related to such a mechanism, p-chlorophenylala...
journal_title:European journal of pharmacology
pub_type: 杂志文章,收录出版
doi:10.1016/s0014-2999(02)02420-2
更新日期:2002-10-25 00:00:00
abstract::The mode of binding of [3H]BQ-123 (cyclo(-D-Trp-D-Asp-[prolyl-3,4 (n)-[3H]]Pro-D-Val-Leu)), an endothelin receptor antagonist radioligand, was evaluated in the human neuroblastoma cell line SK-N-MC at 37 degrees C. Scatchard analysis indicated the presence of a single class of [3H]BQ-123 binding sites with a high affi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00670-3
更新日期:1995-02-14 00:00:00
abstract::Dapagliflozin (DAPA) or canagliflozin (CANA), Na+-dependent glucose co-transporter type 2 (SGLT2) inhibitors, were used for treatment of type II diabetes mellitus. Addition of DAPA or CANA suppressed M-type K+ current (IK(M)) in pituitary tumor (GH3) and pheochromocytoma PC12 cells. The IC50 value for DAPA- or CANA-me...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.173141
更新日期:2020-07-15 00:00:00
abstract::Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.09.050
更新日期:2010-12-15 00:00:00
abstract::In conscious rats, intracerebroventricular (i.c.v.) treatment with the GABA agonist muscimol (1-100 ng) suppressed the pressor responses to ANG II (100 ng i.c.v.) in a dose-dependent and reversible fashion. Treatment i.c.v. with GABA (1-500 micrograms) produced a similar but shorter inhibition. Inhibition of endogenou...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90207-8
更新日期:1983-05-20 00:00:00
abstract::GABA regulates the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) within the GABA receptor-ionophore complex by decreasing the rate of radioligand association and increasing the rate of dissociation but in different ways for the EDTA/water-dialyzed rat brain membranes and a solubilized preparation obtaine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90691-0
更新日期:1985-09-24 00:00:00
abstract::Sanguinarine is a natural isoquinoline alkaloid derived from the root of Sanguinaria canadensis and from other poppy fumaria species, and is known to have a broad spectrum of pharmacological properties. Here we have found that sanguinarine, at low micromolar concentrations, showed a remarkably rapid killing activity a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.02.035
更新日期:2013-04-05 00:00:00
abstract::[3H]Spiroperidol binding was used to assay dopaminergic receptors in synaptosomal membranes isolated from basal ganglia of cat brain. In addition to the usual filtration, a special centrifugation technique was developed which has some advantages for ligands with high non-specific binding. The specific binding to contr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90568-4
更新日期:1982-04-08 00:00:00