当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type Ca²⁺ channels revealed by Timothy syndrome mutation.

Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type Ca²⁺ channels revealed by Timothy syndrome mutation.

Abstract：

:Dihydropyridine Ca(2+) channel antagonists (DHPs) block Ca(V)1.2 L-type Ca(2+) channels (LTCCs) by stabilizing their voltage-dependent inactivation (VDI); however, it is still not clear how DHPs allosterically interact with the kinetically distinct (fast and slow) VDI. Thus, we analyzed the effect of a prototypical DHP, nifedipine on LTCCs with or without the Timothy syndrome mutation that resides in the I-II linker (L(I)-(II)) of Ca(V)1.2 subunits and impairs VDI. Whole-cell Ba(2+) currents mediated by rabbit Ca(V)1.2 with or without the Timothy mutation (G436R) (analogous to the human G406R mutation) were analyzed in the presence and absence of nifedipine. In the absence of nifedipine, the mutation significantly impaired fast closed- and open-state VDI (CSI and OSI) at -40 and 0 mV, respectively, but did not affect channels' kinetics at -100 mV. Nifedipine equipotently blocked these channels at -80 mV. In wild-type LTCCs, nifedipine promoted fast CSI and OSI at -40 and 0 mV and promoted or stabilized slow CSI at -40 and -100 mV, respectively. In LTCCs with the mutation, nifedipine resumed the impaired fast CSI and OSI at -40 and 0 mV, respectively, and had the same effect on slow CSI as in wild-type LTCCs. Therefore, nifedipine has two mechanistically distinct effects on LTCCs: the promotion of fast CSI/OSI caused by L(I-II) at potentials positive to the sub-threshold potential and the promotion or stabilization of slow CSI caused by different mechanisms at potentials negative to the sub-threshold potential.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Sheng X,Nakada T,Kobayashi M,Kashihara T,Shibazaki T,Horiuchi-Hirose M,Gomi S,Hirose M,Aoyama T,Yamada M

doi

10.1016/j.ejphar.2012.04.029

subject

Has Abstract

pub_date

2012-06-15 00:00:00

pages

15-23

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(12)00363-9

journal_volume

685

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF PHARMACOLOGY文献大全
  • Ryanodine and an iodinated analog: doxorubicin effects on binding and Ca2+ accumulation in cardiac sarcoplasmic reticulum.

    abstract：:An 125I-iodinated ryanodine analog, modified by attaching an iodo-Cbz-beta-alanyl group to the C10eq hydroxy of ryanodine (iodo-carbobenzyloxy-beta-alanyl-ryanodine), binds to cardiac sarcoplasmic reticulum Ca2+ release channels with equal affinity as [3H]ryanodine. In the present study, both iodo-Cbz-beta-alanyl-ryan...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0922-4106(94)90061-2

    authors： Bowling N,Mais DE,Gerzon K,Watanabe AM

    更新日期：1994-08-16 00:00:00

  • Synthesis and pharmacology of a prohormone angiotensin antagonist.

    abstract：:A prohormone angiotensin antagonist, Sarcosyl1-Alanyl8-angiotensin I (Sar1-Ala8-A-I) was synthesized and its pharmacological properties were evaluated in three biological systems. It was found to be a good inhibitor in vivo in the rat blood pressure assay, somewhat less active in guinea pig ileum and a relatively weak...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(79)90421-7

    authors： Chiu AT,Sutherland JC Jr,Day AR,Freer RJ

    更新日期：1979-02-15 00:00:00

  • Origin of the hypotensive and sympathoinhibitory effect of morphinomimetic agents.

    abstract：:In vagotomized dogs, lesions of the lateral reticular nucleus (LRN) region did not change arterial blood pressure and sympathetic nerve activity. The hypertensive and tachycardic responses elicited by section of both carotid sinus nerves and both vagus nerves were not altered. However the sympathoinhibitory component ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(83)90167-x

    authors： Laubie M,Schmitt H

    更新日期：1983-08-05 00:00:00

  • Role of RhoA-ROCK signaling in Parkinson's disease.

    abstract：:Parkinson's disease (PD) is a complex and widespread neurodegenerative disease characterized by depletion of midbrain dopaminergic (DA) neurons. Key issues are the development of therapies that can stop or reverse the disease progression, identification of dependable biomarkers, and better understanding of the pathoph...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejphar.2020.173815

    authors： Iyer M,Subramaniam MD,Venkatesan D,Cho SG,Ryding M,Meyer M,Vellingiri B

    更新日期：2020-12-17 00:00:00

  • Effects of baclofen on amino acid release.

    abstract：:This study showed the effects of baclofen on endogenous excitatory (Glu and Asp) and non-excitatory (Tau, Gly and Ala) amino acid release. (A) Release was stimulated by K+ 30 mM in rat frontal cortex slices in vitro (evoked release in ng/g tissue per 5 min): 3739 +/- 215 (Asp), 3429 +/- 357 (Glu), 763 +/- 181 (Tau), 9...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(92)94813-b

    authors： Losada ME,Acosta GB

    更新日期：1992-11-24 00:00:00

  • Induction of cytochrome P450 1A1 expression by ginsenoside Rg1 and Rb1 in HepG2 cells.

    abstract：:Transcriptional activation of the human CYP1A1 gene (coding for cytochrome P450 1A1) is mediated by the aryl hydrocarbon receptor. In the present study we have examined interaction of the ginsenoside Rg1 and Rb1 with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor in HepG2 cells. RT-PCR was...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2008.10.057

    authors： Wang Y,Ye X,Ma Z,Liang Q,Lu B,Tan H,Xiao C,Zhang B,Gao Y

    更新日期：2008-12-28 00:00:00

  • Characterization of histamine H1-receptors on astrocytes in primary culture: [3H]mepyramine binding studies.

    abstract：:The characteristics of histamine H1-receptors on astrocytes from the cerebral cortex of newborn rats in primary culture were analyzed with a [3H]mepyramine binding assay, and compared with those in the cerebral cortex. The apparent dissociation constant (KD) of [3H]mepyramine binding, the apparent inhibition constants...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(89)90007-1

    authors： Inagaki N,Fukui H,Taguchi Y,Wang NP,Yamatodani A,Wada H

    更新日期：1989-11-28 00:00:00

  • Effects of papaverine on isolated rabbit papillary muscle.

    abstract：:The effect of papaverine on the positive inotropic response to isopreqaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose-response curve for isoprenaline was shifted to the left by papaverine (3 times 10- minus 6 to...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(75)90102-8

    authors： Endoh M,Schümann HJ

    更新日期：1975-02-01 00:00:00

  • Characterization of capsaicin-induced, capsazepine-insensitive relaxation of ileal smooth muscle of rats.

    abstract：:The mechanisms underlying the capsaicin-induced relaxation of the acetylcholine- as well as KCl-contraction were studied by measuring isometric force and phosphorylation of 20-kDa regulatory light chain subunit of myosin (MLC(20)) in ileal longitudinal smooth muscles of rats. Capsaicin relaxed acetylcholine- and KCl-s...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2004.01.014

    authors： Fujimoto S,Mori M

    更新日期：2004-03-08 00:00:00

  • Direct evidence for an angiotensin AT1 receptor type in rat vas deferens.

    abstract：:Physiological experiments suggest that the angiotensin AT1 receptor type predominates in rat vas deferens. Membrane binding experiments, using 125I-[Sarl,Ile8]angiotensin II, confirm the presence of angiotensin AT1 receptors and the absence of angiotensin AT2 receptors in this tissue. Angiotensin II and the angiotensi...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(98)00380-x

    authors： Maletínská L,Slaninová J,Kunes J,Zelezná B

    更新日期：1998-06-26 00:00:00

  • Therapeutic administration of Y-40138, a multiple cytokine modulator, inhibits concanavalin A-induced hepatitis in mice.

    abstract：:Concanavalin A-induced hepatitis is often used as a model of liver injury. In this model, plasma tumor necrosis factor-alpha (TNF-alpha) level increased in concanavalin A-injected mice. Prophylactic treatment with Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl, significantl...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2005.08.060

    authors： Fukuda T,Mogami A,Hisadome M,Komatsu H

    更新日期：2005-10-31 00:00:00

  • Alpha 1-adrenoceptor stimulation increases intracellular pH and Ca2+ in cardiomyocytes through Na+/H+ and Na+/Ca2+ exchange.

    abstract：:The effects of alpha 1-adrenergic stimulation on intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were investigated in isolated rat cardiomyocytes with fluorescence dyes, BCECF and fura-2, respectively. In the presence of 5 or 25 mM HCO3- norepinephrine (NE) increased pHi in a dose-dependent manner. Intracellul...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(90)94057-5

    authors： Iwakura K,Hori M,Watanabe Y,Kitabatake A,Cragoe EJ Jr,Yoshida H,Kamada T

    更新日期：1990-09-04 00:00:00

  • Relative agonist potencies of C2-substituted analogues of adenosine: evidence for adenosine A2B receptors in the guinea pig aorta.

    abstract：:Nine C2-substituted adenosine analogues that are potent and selective for the A2-adenosine receptor were tested for their ability to induce relaxations of the guinea pig aorta. Compounds tested were 2-phenylethoxyadenosine (PEA), 2-phenylethoxy-5'-N-ethylcarboxamidoadenosine (PENECA), 2-cyclohexylethoxyadenosine (CEA)...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(92)90365-b

    authors： Martin PL

    更新日期：1992-06-05 00:00:00

  • GABA modulates the release of dopamine and acetylcholine from rat caudate nucleus slices.

    abstract：:The effects of GABA on depolarization-induced (26 mM K+) release of radiolabeled dopamine (DA) and acetylcholine (ACh) from slices of rat caudate nucleus were examined with a superfusion method. GABA, in concentrations of 10(-5)--10(-3) M, dose-dependently enhanced the release of DA, either accumulated by high-affinit...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(79)90101-8

    authors： Stoof JC,Den Breejen EJ,Mulder AH

    更新日期：1979-07-15 00:00:00

  • Multiple types of receptors for atrial natriuretic peptide.

    abstract：:The binding of atrial natriuretic peptide (ANP) to olfactory bulb, pituitary anterior lobe and thymus gland membranes was examined. [125I]ANP (rat, 99-126) bound specifically to the three types of membranes. However, the affinity for ANP receptor in olfactory bulb was much higher than those in either pituitary or thym...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(89)90293-8

    authors： Agui T,Kurihara M,Saavedra JM

    更新日期：1989-03-21 00:00:00

  • Mechanisms underlying the inhibitory effect of dibutyryl cyclic AMP in vascular smooth muscle.

    abstract：:The mechanism by which dibutyryl cyclic AMP (db-cAMP) induces vasodilatation was examined in isolated rat aorta. The contraction induced by norepinephrine (NE) was more sensitive to the inhibitory effect of db-cAMP than that induced by high K+, and the contraction induced by lower concentrations of each stimulant was ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(92)90385-h

    authors： Abe A,Karaki H

    更新日期：1992-02-18 00:00:00

  • Differential effects of chronic dopamine D1 and D2 receptor agonists on rotational behavior and dopamine receptor binding.

    abstract：:The effects of chronic continuous and intermittent administration of the dopamine D1 receptor agonist SKF 38393 or the D2 receptor agonist quinpirole on rotational behavior and dopamine receptor binding were examined in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Continuous and interm...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(93)90476-x

    authors： Engber TM,Marin C,Susel Z,Chase TN

    更新日期：1993-06-04 00:00:00

  • Dose-dependent effects of adenosine antagonists on tacrine-induced tremulous jaw movements.

    abstract：:The present study examines the effect of three adenosine receptor antagonists on tremulous jaw movements (TJMs), an animal model of tremor. Forty-five rats were pre-treated with one adenosine antagonist: caffeine (0.0, 5.0, or 10.0 mg/kg; non-selective adenosine receptor antagonist), 8-cyclopentyltheophylline (CPT; 0....

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2018.06.004

    authors： Johnson JA,Montgomery AP,Starr ER,Ludwig J,Trevitt J

    更新日期：2018-08-15 00:00:00

  • Inhibitory actions of ropivacaine on tumor necrosis factor-alpha-induced leukocyte adhesion and tissue accumulation in vivo.

    abstract：:We have examined the effect of ropivacaine, a local anesthetic, on leukocyte-endothelium interactions induced by tumor necrosis factor-alpha (TNF-alpha) in vivo by the use of intravital microscopy in the mouse cremaster microcirculation. It was found that ropivacaine markedly reduced venular leukocyte adhesion and tis...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(00)00108-4

    authors： Zhang XW,Thorlacius H

    更新日期：2000-03-24 00:00:00

  • Effects of nicotine on K+ channel currents in vascular smooth muscle cells from rat tail arteries.

    abstract：:Intake of nicotine has been related in many cases to acute or chronic hypertension. Using the patch-clamp technique the effect of nicotine on voltage-dependent K+ channel currents in rat tail artery smooth muscle cells was studied. Nicotine at concentrations of 1-100 microM or 0.3-3 mM increased or decreased, respecti...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(98)00833-4

    authors： Tang G,Hanna ST,Wang R

    更新日期：1999-01-08 00:00:00

  • Neuroprotective effects of salvianolic acid B on an Aβ25-35 peptide-induced mouse model of Alzheimer's disease.

    abstract：:Salvianolic acid B (SalB) is a polyphenolic compound found in Salvia miltiorrhiza Bunge that has several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether SalB has neuroprotective effects in an amyloid β (Aβ) peptide-induced Alzheimer's disease mouse model. Mice were injected ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2013.02.015

    authors： Lee YW,Kim DH,Jeon SJ,Park SJ,Kim JM,Jung JM,Lee HE,Bae SG,Oh HK,Son KH,Ryu JH

    更新日期：2013-03-15 00:00:00

  • An in vitro study of histamine on the pulmonary artery of the Wistar-Kyoto and spontaneously hypertensive rats.

    abstract：:The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via hist...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(03)01759-x

    authors： Lau WH,Kwan YW,Au AL,Cheung WH

    更新日期：2003-05-30 00:00:00

  • Blockade of endothelin ET(A), but not thromboxane, receptors offsets the cyclosporine-evoked hypertension and interrelated baroreflex and vascular dysfunctions.

    abstract：:The impairment of arterial baroreceptor and vasodilator functions are two major contributors to the hypertensive action of cyclosporine (CSA). In this study, in vivo and in vitro pharmacological studies were performed to investigate whether these effects of CSA are differentially modulated by endothelin and thromboxan...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2014.01.034

    authors： Nasser SA,Elmallah AI,Sabra R,Khedr MM,El-Din MM,El-Mas MM

    更新日期：2014-03-15 00:00:00

  • C-fibers, but not the transient potential receptor vanilloid 1 (TRPV1), play a role in experimental allergic airway inflammation.

    abstract：:The activation of C-fibers in the airways induces coughing, mucus production and bronchoconstriction, which are also symptoms of airway diseases. In this study, we evaluated the role of the C-fibers and the TRPV1 (transient receptor potential vanilloid 1) receptor in an experimental mouse model of allergic airway infl...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2011.04.027

    authors： Rogerio AP,Andrade EL,Calixto JB

    更新日期：2011-07-15 00:00:00

  • Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration.

    abstract：:18-Methoxycoronaridine, a novel iboga alkaloid congener, reduces drug self-administration in animal models of addiction. Previously, we proposed that these effects are mediated by the ability of 18-methoxycoronaridine to inhibit nicotinic alpha3beta4 acetylcholine receptors. In an attempt to identify more potent 18-me...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2004.03.062

    authors： Pace CJ,Glick SD,Maisonneuve IM,He LW,Jokiel PA,Kuehne ME,Fleck MW

    更新日期：2004-05-25 00:00:00

  • The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the alpha2A-adrenoceptor gene.

    abstract：:Alpha(2A)-Adrenoceptors mediate the antinociceptive effects of alpha(2)-adrenoceptor agonists in mice, and analgesic synergism between noradrenergic and opioidergic mechanisms has been reported to be lacking in mice devoid of functional alpha(2A)-adrenoceptors. We investigated whether the antinociceptive actions of op...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2005.10.029

    authors： Ozdoğan UK,Lähdesmäki J,Scheinin M

    更新日期：2006-01-04 00:00:00

  • Long-term interactions between endogenous and exogenous opiates.

    abstract：:The in vitro biological effect of various opiates was studied in the guinea pig ileum bioassay. Besides their direct, immediate effect, certain opiates induced sensitivity changes which persisted after their removal and the complete recovery of the preparation. These specific, asymmetrical interactions may represent l...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(80)90488-4

    authors： Sarne Y,Gothilf Y,Weissman BA

    更新日期：1980-03-07 00:00:00

  • Reduction of renal lipid content and proteinuria by a PPAR-γ agonist in a rat model of angiotensin II-induced hypertension.

    abstract：:An excess of lipids may accumulate in the kidney in conditions such as diabetes and hypertension, and can potentially cause renal injury. We previously reported that an infusion of angiotensin II into a rat induced deposition of lipids in the renal tubular epithelial cells. Here we have examined the effect of pioglita...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2012.02.027

    authors： Sakamoto A,Hongo M,Saito K,Nagai R,Ishizaka N

    更新日期：2012-05-05 00:00:00

  • The involvement of DAMPs-mediated inflammation in cyclophosphamide-induced liver injury and the protection of liquiritigenin and liquiritin.

    abstract：:Cyclophosphamide (CPA) is a chemotherapeutic drug widely used in the treatment of breast cancer or leukemia in clinic. However, CPA was reported to have hepatotoxicity. This study aims to observe the engaged mechanism of CPA-induced liver injury in mice and the protection of liquiritin (LQ) and liquiritigenin (LG). Li...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2019.172421

    authors： Chen M,Zhang C,Zhang J,Kai G,Lu B,Huang Z,Ji L

    更新日期：2019-08-05 00:00:00

  • SP600125 blocks the proteolysis of cytoskeletal proteins in apoptosis induced by gas signaling molecule (NO) via decreasing the activation of caspase-3 in rabbit chondrocytes.

    abstract：:NO plays a key role in the pathological mechanisms of articular diseases. As cytoskeletal proteins are responsible for the polymerization, stabilization, and dynamics of the cytoskeleton network, we investigated whether cytoskeletal proteins are the intracellular pathological targets of NO. We aimed at clarifying whet...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2018.01.032

    authors： Kao XB,Chen Q,Gao Y,Fan P,Chen JH,Wang ZL,Wang YQ,Chen YN,Yan YP

    更新日期：2018-04-05 00:00:00