Abstract：
:The antihypertensive drug doxazosin has been associated with an increased risk for congestive heart failure and cardiomyocyte apoptosis. Human ether-a-go-go-related gene (hERG) K(+) channels, previously shown to be blocked by doxazosin at therapeutically relevant concentrations, represent plasma membrane receptors for the antihypertensive drug. To elucidate the molecular basis for doxazosin-associated pro-apoptotic effects, cell death was studied in human embryonic kidney cells using three independent apoptosis assays. Doxazosin specifically induced apoptosis in hERG-expressing HEK cells, while untransfected control groups were insensitive to treatment with the antihypertensive agent. An unexpected biological mechanism has emerged: binding of doxazosin to its novel membrane receptor, hERG, triggers apoptosis, possibly representing a broader pathophysiological mechanism in drug-induced heart failure.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Thomas D,Bloehs R,Koschny R,Ficker E,Sykora J,Kiehn J,Schlömer K,Gierten J,Kathöfer S,Zitron E,Scholz EP,Kiesecker C,Katus HA,Karle CAdoi
10.1016/j.ejphar.2007.10.051subject
Has Abstractpub_date
2008-01-28 00:00:00pages
98-103issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(07)01207-1journal_volume
579pub_type
杂志文章abstract：:Polygonum tinctorium Lour. (P. tinctorium) is known to have the ability to suppress inflammation. We attempted to isolate the active compounds from P. tinctorium based on their inhibitory effects on the production of interferon-gamma, which is a well-known inflammatory cytokine. We thus isolated indirubin, an isomer o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:Chronic lithium treatment was examined for effects on the blood pressure of spontaneously hypertensive rats (SHRs). Treated rats were allowed continuous access to a pelleted lithium diet (1.7 g LiCl (40 mmol)/kg diet) for 21 days. Control SHRs were fed a similar diet lacking the lithium. Two groups of control rats wer...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90112-6
更新日期：1981-12-17 00:00:00
abstract：:The Ah receptor (AhR) mediates many, if not all, of the toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons. Although wide variations in species sensitivity to these compounds have been observed, numerous biochemical and physiochemical charac...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(92)90016-6
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abstract：:In rat carotid arteries isolated 2 weeks after balloon denudation, a significant neointima developed with little change in medial size. Associated with this neointimal hyperplasia was a marked decrease in contraction to various agents including angiotensins I and II, big endothelin-1, endothelin-1, norepinephrine, phe...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90610-6
更新日期：1994-04-11 00:00:00
abstract：:Hruska et al. (1980) reported that hypophysectomy prevented the onset of dopamine receptor supersensitivity. We have repeated this investigation administering haloperidol (0.75 mg/day) or sulpiride (2 X 15 mg/day) or saline for 17 days, followed by a 3 day drug washout period, to sham-operated or hypophysectomised rat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:To test the hypothesis that serotonergic modulation of the effects of phencyclidine (PCP) are due to circuit- rather than receptor-based interactions between glutamatergic and serotonergic systems, multivariate profiles of rat behavior were assessed after treatments with the 5-hydroxytryptamine (5-HT) 5-HT2 receptor a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01557-4
更新日期：1998-02-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.11.019
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：2016-11-05 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/s0014-2999(98)00545-7
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.02.047
更新日期：2018-05-05 00:00:00
abstract：:The effect of indomethacin, acetyl salicylic acid and niflumic acid on the chemotaxis and random migration of rat polymorphonuclear leucocytes (PMN) was investigated with a modified Boyden chamber technique under various experimental conditions (two cell sources, administration of drugs in vivo or incubation in vitro,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(01)01319-x
更新日期：2001-10-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90291-5
更新日期：1975-06-01 00:00:00
abstract：:In bovine aortic endothelial cells (BAEC), pertussis toxin (PTx) ADP-ribosylated two major substrates with apparent molecular masses of 40 and 41 kDa, whereas cholera toxin (CTx) ADP-ribosylated two other substrates of 44 and 50 kDa. [alpha-32P]GTP bound to three bands in the 22-27 kDa range. Immunoblot analysis revea...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90068-k
更新日期：1993-10-15 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2008.04.056
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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更新日期：2006-05-24 00:00:00
abstract：:The cell adhesion molecules N-, VE- and OB-cadherin have been implicated as regulators of tumor growth and metastasis. We discuss evidence that N- and VE-cadherin play a key role in promoting blood vessel formation and stability, processes which are essential for tumor growth. Secondly, we describe the potential invol...
journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.03.059
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abstract：:The effect of the antipsychotic peptide, Org 5878 (desenkephalin-gamma-endorphin, beta-endorphin-(6-17), on local cerebral glucose utilization was studied in freely moving male Wistar rats. Org 5878 (20 micrograms/kg, i.v.) or saline were given acutely and local cerebral glucose utilization was measured in 116 brain s...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:To elucidate the mechanism of age-related changes in the cardiovascular function stimulated with angiotensin II, we examined the effects of angiotensin II on the coronary flow, production of nitric oxide (NO) and prostacyclin, and on the cardiac function in the Langendorff-perfused young and aged rats' hearts. Angiote...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:Cocaine and a cocaine analog, WIN 36,065-2, were administered daily for 3 or 4 days. Both compounds developed sensitization to their locomotor stimulatory effects, with similarly shaped dose-response curves. Dosages giving optimal sensitization were 25 mg/kg per day for cocaine and 3 mg/kg for WIN 35,065-2. At 40 mg/k...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1986-10-14 00:00:00
abstract：:The modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is increasingly recognized as an important posttranslational modification that modulates cellular function. Recent studies suggested that augmentation of O-GlcNAc levels increase cell survival following stress. Salidroside, one of the active com...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.04.012
更新日期：2009-06-24 00:00:00
abstract：:In cross-chopped slices from rat thalamus and in the presence of 10 mM LiCl, noradrenaline stimulated the accumulation of [3H]inositol phosphates with [3H]inositol monophosphates ([3H]IP1) being the major product detected (86 +/- 2% of total [3H]inositol phosphates). Noradrenaline-induced [3H]IP1 accumulation was conc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00781-9
更新日期：1996-12-27 00:00:00
abstract：:Baicalin has been reported to protect against liver injury in iron-overload mice, however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In this study, we systematically studied the protective effect of baicalin on iron overload induced liver injury, as well as the underl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.01.010
更新日期：2012-04-05 00:00:00
abstract：:Administration of dihydrocapsaicin to rats resulted in a dose-dependent (0.5-10 mg/kg s.c.) hypothermia. Dihydrocapsaicin was approximately 65% more effective in producing hypothermia than capsaicin. Desensitization and cross-tolerance occurred to the hypothermic effects of both capsaicin and dihydrocapsaicin. Repeate...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90263-1
更新日期：1982-09-24 00:00:00
