Abstract：
:The anticancer drugs camptothecin (CPT) and topotecan (TPT) are known DNA topoisomerase I inhibitors which cause DNA damage and lead to cell death. In this study we provide evidence that CPT and TPT also interfere with the elements of cytoskeleton - microtubules and actin filaments which could be partly responsible for their cytotoxic properties. CPT and TPT apparently affected microtubule structures in living cells (Hela and U2OS) and inhibited tubulin polymerization in vitro with IC50 values of 74.57±9.96µM and 121.55±58.68µM, respectively. TPT significantly affected the nucleation and growth phase during the microtubule assembly in vitro, whereas the mode of action of CPT was different in that it specifically affected the 'tread milling' of polymerized microtubules. Cell cycle effects of CPT and TPT varied with their concentrations. CPT and TPT induced G2/M arrest and promoted the population to 76.94±11.20% and 83.91±2.43% at a concentration of 9.4nM and 46.9nM, respectively. As the concentration increased, cells were blocked in S phase with a dose-dependent reduction in G2/M population. In addition, CPT and TPT exhibited a certain effect on actin filaments by reducing the mass of actin filaments. The interactions of CPT and TPT with microtubules and actin filaments present new insights into their modes of action.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wang X,Tanaka M,Krstin S,Peixoto HS,Moura CCM,Wink Mdoi
10.1016/j.ejphar.2016.07.044subject
Has Abstractpub_date
2016-10-15 00:00:00pages
265-274eissn
0014-2999issn
1879-0712pii
S0014-2999(16)30485-Xjournal_volume
789pub_type
杂志文章abstract：:In cultured rat heart muscle cells, reversible long-term ATP depletion induces a decrease in beta-adrenoceptor density and a fall in isoproterenol- as well as forskolin-stimulated cAMP formation. However, isoproterenol-stimulated adenylyl cyclase activity in membrane preparations is not reduced after ATP depletion. Th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(91)90104-p
更新日期：1991-11-13 00:00:00
abstract：:Recent reports have provided evidence for a new concept that in small resistance arteries α1D-adrenoceptor-mediated contraction is intimately linked to pannexin-1 (Px1) hemichannels that open to allow the release of ATP, from the smooth muscle effector cell, that acts back on P2Y purinoceptors to cause contraction. Th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.01.024
更新日期：2015-03-05 00:00:00
abstract：:Capsaicin (1-3 microM) and electrical stimulation of mesenteric nerves in the presence of hexamethonium and guanethidine antidromically stimulate extrinsic sensory nerve fibers to produce a specific slow depolarizing response of myenteric neurons and a contractile response of muscles in the isolated guinea-pig ileum, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90092-v
更新日期：1993-06-11 00:00:00
abstract：:Mouse peritoneal inflammatory macrophages have a saturable binding site for [3H]flunitrazepam with a KD of 43 +/- 7 nM and Bmax of 391 +/- 58 fmol per 10(6) cells, which corresponds to 250 000 sites per cell. The IC50 values for PK 11195, Ro 5-4864, diazepam, flunitrazepam, clonazepam, ethyl-beta carboline 3-carboxyla...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90059-1
更新日期：1984-11-27 00:00:00
abstract：:Naloxone, a competitive antagonist of opioid receptors, and placebo (dextrose 5% in water (D5W) were administered on separate days to healthy normotensive (NT) male volunteers and to male patients with essential hypertension (HT). A single-blind, placebo-controlled, cross-over design was employed. Increasing doses of ...
journal_title：European journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1016/0014-2999(86)90048-8
更新日期：1986-07-31 00:00:00
abstract：:The effects of angiotensin II (AII) and angiotensin III (AIII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of total body venous tone, in the presence and absence of [Sar1,Ile8]AII in conscious rats were examined. The infusion of AII caused dose-dependent increases in MAP and ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90074-4
更新日期：1987-10-27 00:00:00
abstract：:Rats were administered haloperidol, clozapine, raclopride, or no drug for either 28 days or 8 months and then withdrawn from drug treatment for 3 weeks. Oral movements were repeatedly recorded, both by a human observer and by a computerized video analysis system which determined mouth openings and closings, or compute...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90077-j
更新日期：1990-06-08 00:00:00
abstract：:Transient activation of the outward K+ current caused by a rise in the cytosolic free Ca2+ concentration, [Ca2+]i was the predominant change in plasma membrane ion flux during the first phase of thyrotropin-releasing hormone (TRH) action on pituitary cells. Following the intracellular application of inhibitors of 1,2-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(89)90046-1
更新日期：1989-03-07 00:00:00
abstract：:Mitiglinide (KAD-1229), a new anti-diabetic drug, is thought to stimulate insulin secretion by closing the ATP-sensitive K+ (K(ATP)) channels in pancreatic beta-cells. However, its selectivity for the various K(ATP) channels is not known. In this study, we examined the effects of mitiglinide on various cloned K(ATP) c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01412-1
更新日期：2001-11-09 00:00:00
abstract：:The renal vascular effects of dopaminomimetics were studied in the isolated perfused rat kidney after pretreatment with 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) to 3 x 10(-6) M). Under these conditions, our criterion for vascular dopam...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90157-1
更新日期：1982-10-15 00:00:00
abstract：:Opiate agonists exhibiting selectivity for mu, kappa, sigma, and delta opiate receptors were microinjected into the periaqueductal gray region (PAG) of the brain of rats to determine the receptor subtype(s) associated with the initiation of descending pain inhibition. The spinally organized, heat nociceptive tail-flic...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90145-8
更新日期：1988-10-26 00:00:00
abstract：:Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanism...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.07.057
更新日期：2008-10-24 00:00:00
abstract：:Several structural analogs of mazindol were tested as inhibitors of the uptake of [3H] dopamine in rat neostriatum, of [3H] norepinephrine in rat occipital cortex and of [3H] serotonin in whole rat brain. A rather wide range of potencies was observed but a number of the drugs were even more potent than mazindol as upt...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90030-3
更新日期：1981-05-08 00:00:00
abstract：:7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepine-2(3H)-one (CGP-37157) inhibits mitochondrial Na(+)-Ca(2+) exchange. It is often used as an experimental tool for studying the role of the mitochondrial Na(+)-Ca(2+) exchanger in Ca(2+) signaling. Because the selectivity of CGP-37157 in adult cardiomyocytes ha...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.09.013
更新日期：2006-12-15 00:00:00
abstract：:The effects of N-(aminoiminomethyl)-1, 4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid (SM-20550), a novel potent Na(+)/H(+) exchanger, and nicorandil, a K(+) channel opener with nitrate-like activity, were studied in a myocardial ischemia and reperfusion injury model. Anesthetized rabbits underwent occlusion ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00610-5
更新日期：2000-09-15 00:00:00
abstract：:We evaluated the inhibitory activity of a novel prostacyclin analog, OP-2507 (15-cis-(4-n-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deo xy-6,9 alpha- nitriloprostaglandin F1 methyl ester) on the brain edema induced by occlusion of the middle cerebral artery in cats. Middle cerebral artery occlusion for 4h caused a d...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90836-9
更新日期：1988-07-26 00:00:00
abstract：:The functions of the 5-HT(4) receptor in the gastrointestinal tract are complex, depending on the species and anatomical regions, and localization of the receptor was not clear. The present study attempted to examine the localization of the 5-HT(4) receptor in the colon of human for comparison with that in guinea pig ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00642-1
更新日期：1999-11-03 00:00:00
abstract：:We investigated the effects of KF19514 (5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4 (5H)-one) on bronchoconstriction and allergic inflammation in guinea pigs and on tumor necrosis factor-alpha production in mice. KF19514 inhibited phosphodiesterase 4 (IC50 = 0.40 microM) and phosphodiesterase 1 (...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01063-7
更新日期：1997-07-30 00:00:00
abstract：:To assess the role of the alpha 7 neuronal nicotinic acetylcholine receptor in the discriminative stimulus properties of (-)-nicotine, this study investigated the ability of the alpha 7 receptor antagonist methyllycaconitine to modulate the nicotine cue. In rats trained to discriminate (-)-nicotine from saline, intrap...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00010-6
更新日期：1996-04-22 00:00:00
abstract：:Disturbances in myocyte calcium homeostasis are hypothesized to be one cause for cardiac arrhythmia. The full development of this hypothesis requires (i) the identification of all sources of arrhythmogenic calcium and (ii) an understanding of the mechanism(s) through which calcium initiates arrhythmia. To these ends w...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.12.020
更新日期：2014-02-05 00:00:00
abstract：:The effects of baicalein, a flavonoid, and alpha-tocopherol (vitamin E) on lipid peroxidation in rat forebrain homogenates, on free radical scavenging action against diphenyl-p-picrylhydrazyl (DPPH), and on 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice were studied. Baicalein inhibited lipid peroxi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90700-e
更新日期：1992-10-20 00:00:00
abstract：:The effects of the metabotropic glutamate (mGlu) receptor agonists (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or 1S,3R-ACPD on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic responses have been investigated in vitro in CA1 pyramidal cells of rat hippocampal slices. Bath application...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00223-8
更新日期：1995-08-04 00:00:00
abstract：:Recent data show that corticolimbic expression of the effector immediate early gene Arc is up-regulated by standard antidepressant drugs. Here, we tested the effect upon Arc expression of a novel antidepressant and selective 5-hydroxytryptamine/noradrenaline reuptake inhibitor (SNRI), (-)1-(1-dimethylaminomethyl) 5-me...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.03.002
更新日期：2004-04-12 00:00:00
abstract：:Neuropeptides represent by far the most common signalling molecules in the central nervous system. They are involved in a wide range of physiological functions and can act as neurotransmitters, neuromodulators or hormones in the central nervous system and in the periphery. Accumulating evidence during the past 40 year...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2009.09.070
更新日期：2010-01-10 00:00:00
abstract：:Methoctramine, a selective M2 alpha muscarinic receptor antagonist, was examined for its ability to inhibit carbachol-induced drinking in the rat. Intracerebroventricularly (i.c.v.) administered methoctramine was devoid of activity up to a dose of 100 nmol/rat, whereas higher doses were toxic under our experimental co...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90213-6
更新日期：1989-04-25 00:00:00
abstract：:Guinea-pig tracheal smooth muscle possesses an inhibitory non-adrenergic, non-cholinergic (i-NANC) innervation and the neurotransmitters involved in this response may be vasoactive intestinal peptide (VIP) and nitric oxide (NO). Since i-NANC mechanisms may co-exist with cholinergic nerves we have investigated whether ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90689-f
更新日期：1993-01-26 00:00:00
abstract：:The effects of the dopamine D2 receptor agonist quinpirole (LY 171555) on locomotor activity and margin time (thigmotaxis or wall-hugging) were measured for 2 h in rats injected either s.c. (vehicle, 0.02, 2.0 mg/kg) or directly into either the dorsal striatum or nucleus accumbens (vehicle, 0.1, 1.0, 10, 20 or 40 micr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90091-h
更新日期：1992-04-07 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that contracts most smooth muscles. Although S1P has been shown to contract bladder smooth muscle, the mechanism(s) by which S1P initiates contraction has not been extensively investigated. The goal of this study was to determine if S1P-induced force generation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.10.004
更新日期：2013-11-15 00:00:00
abstract：:Unexpectedly, it was observed that the P2-purinoceptor antagonist, suramin (10 microM to 1 mM), reversed the muscle paralysis caused by structurally unrelated non-depolarizing relaxants. Suramin competitively reversed the blocking action of pancuronium. Both the pre- and postsynaptic blockade of nicotinic receptors by...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90211-l
更新日期：1992-05-27 00:00:00
abstract：:In rats, tolerance to the analgesic effect of intraventricular substance P (SP) develops quickly. In rats made tolerant to [D-Ala2, D-Leu5]enkephalin the analgesic efficacy of SP is reduced significantly. The latter result suggests some overlap in the sites of action of SP and [D-Ala2,D-Leu5] enkephalin. Since SP seem...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90119-5
更新日期：1984-02-10 00:00:00
