Abstract：
:Thirty percent of osteosarcoma patients die within 5 years. New agents that induce apoptosis of osteosarcoma cells might be therapeutically useful. Here, we characterized the apoptotic mechanism induced by capsaicin in G292 osteosarcoma cells. Our results show that capsaicin induces an increase in the cytosolic Ca(2+) concentration which is independent of the extracellular Ca(2+) concentration and depletes intracellular Ca(2+) stores, suggesting the presence of endoplasmic reticulum transient receptor potential vanilloid receptor type 1. Capsaicin also activates the mitochondrial caspase 3-dependent death cascade. Rapamycin, an inhibitor of mammalian target of rapamycin, evokes autophagy, as do capsaicin or thapsigargin, a sarco(endo)plasmic reticulum Ca(2+) ATPase inhibitor that causes Ca(2+) store depletion. Capsaicin-induced cell death is completely inhibited by co-treatment with the pan-caspase inhibitor Z-VAD-fmk and increased by the autophagy inhibitor 3-methyladenine, suggesting the existence of an autophagy-dependent anti-apoptotic mechanism. Capsaicin also induces ERK phosphorylation, which acts as a downstream effector of autophagy. 3-Methyladenine or PD98059, an ERK kinase inhibitor, restores capsaicin-induced cell death in the presence of Z-VAD-fmk, suggesting that inhibition of autophagy activates a second cell death pathway that is caspase-independent. Taken together, our data show that capsaicin causes Ca(2+) depletion of intracellular Ca(2+) stores and simultaneously activates the mitochondrial caspase-dependent death cascade and autophagy-dependent ERK activation and that the latter counteracts a second death signaling pathway that is caspase-independent.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Chien CS,Ma KH,Lee HS,Liu PS,Li YH,Huang YS,Chueh SHdoi
10.1016/j.ejphar.2013.08.011subject
Has Abstractpub_date
2013-10-15 00:00:00pages
350-60issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(13)00601-8journal_volume
718pub_type
杂志文章abstract：:Previous work from our laboratory has indicated that ovine prolactin can produce a rapid stimulation (within 1 h) of dopamine release from nigrostriatal and mesolimbic dopaminergic neurons of male rats. In the present experiment we attempted to determine whether this effect of prolactin was a function of an increase i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90361-0
更新日期：1989-08-03 00:00:00
abstract：:Pancreatic adenocarcinoma is a leading cause of cancer death in the United States and represents a challenging chemotherapeutic problem. The pharmacological control of angiogenesis might represent a novel approach to the management of pancreas cancer, since the pathological development of vascular supply is a critical...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.07.062
更新日期：2004-09-13 00:00:00
abstract：:The maximal number of binding sites (Bmax) and the equilibrium dissociation constant (KD) values for [3H]PK 11195 binding were determined in the platelet membranes of epileptic patients before and after 4 weeks of carbamazepine (CBZ) treatment, as well as in healthy controls. There was a decrease of 17.1% in the Bmax ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90567-x
更新日期：1987-09-23 00:00:00
abstract：:Increased O-Linked β-N-acetylglucosamine (O-GlcNAc) is observed in several pathologies, and unbalanced O-GlcNAcylation levels favor endothelial dysfunction. Whether augmented O-GlcNAc impacts the uterine artery (UA) function and how it affects the UA during pregnancy remains to be elucidated. We hypothesized that gluc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173133
更新日期：2020-08-05 00:00:00
abstract：:Complete control of emesis caused by cyclophosphamide (CPA) is of immense interest to both patients and physicians. Serotonin 5-HT3- and tachykinin NK1-receptor antagonists are widely used antiemetics in clinic, but they fail to completely control CPA-induced emesis. New antiemetic targets for the full control of CPA-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.09.080
更新日期：2014-01-05 00:00:00
abstract：:We examined the mechanism of endothelin-1-induced contraction in the porcine coronary artery by assessing the changes in myosin light chain phosphorylation and cytosolic Ca2+ concentration ([Ca2+]i) determined by fura-2 and front-surface fluorometry. Endothelin-1 induced a rapid phosphorylation of myosin both in the p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90011-6
更新日期：1994-12-15 00:00:00
abstract：:Corticotropin-releasing factor (CRF) plays an important role in sympathetic regulation. Centrally administered CRF elevates plasma catecholamine levels, resulting in CRF-dependent hypertension and tachycardia. We previously reported that brain thromboxane A2 mediates CRF-induced elevation of plasma adrenaline levels, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172693
更新日期：2019-11-15 00:00:00
abstract：:Several studies have shown that glycine transporter 1 (GlyT1) inhibitors have anxiolytic actions. There are two types of glycine receptor: the strychnine-sensitive glycine receptor (GlyA) and the strychnine-insensitive glycine receptor (GlyB); however, which receptor is the main contributor to the anxiolytic actions o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.11.024
更新日期：2015-01-05 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：:The effects of nicotine, carbachol, hexamethonium and scopolamine were investigated on distress vocalizations (DBs) of acutely isolated domestic chicks. Nicotine attenuated, while the antimuscarinic scopolamine increased the frequency of separation-induced DVs. Furthermore, the stress attenuating effects of nicotine w...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90283-1
更新日期：1981-06-19 00:00:00
abstract：:Nitric oxide (NO) and prostacyclin (PGI(2)) are two of the most important vasodilators produced by endothelial cells, the regulation of NO on PGI(2) production has not been fully clear yet. Polyaspartoyl.L-arginine (PDR) is an L-arginine residue-rich compound with inhibitory effects of platelet aggregation and thrombo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.11.003
更新日期：2008-12-28 00:00:00
abstract：:Stimulation of muscarinic M1-receptors in isolated rabbit vas deferens by McN-A-343 inhibited electrically induced twitch contractions susceptible to competitive blockade by (+)-, (+/-), (-)-telenzepine and pirenzepine (pA2 = 9.12, 8.86, 6.98 and 7.79, respectively). The inhibition of twitch contractions by 10(-6) M M...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90604-5
更新日期：1990-05-03 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
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2009.05.033
更新日期：2009-12-25 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
abstract：:This study examined whether a clinically relevant concentration of the volatile anaesthetic halothane modifies the endothelium-dependent relaxation produced by acetylcholine (3 nM-10 microM), histamine (1 pM-0.1 microM) and anti-human immunoglobulin E (1:1000) in human isolated pulmonary arteries submaximally precontr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)85412-x
更新日期：1997-05-20 00:00:00
abstract：:The mucociliary activity of the rabbit maxillary sinus is increased after exposure to airway irritants such as cigarette smoke and capsaicin. This effect is partly due to a cholinergic reflex but involves an atropine-resistant response probably mediated by the release of tachykinins such as substance P or neurokinin A...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90113-v
更新日期：1993-02-16 00:00:00
abstract：:Recently we have demonstrated that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) constricts rat aortic rings and that this effect is cyclooxygenase- and endothelium-dependent. Incubation of 20-HETE with ram seminal vesicles, a rich source of cyclooxygenase, led to the identification of vasoconstrictor metabolit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90812-v
更新日期：1993-04-22 00:00:00
abstract：:Oxidative stress has been implicated in the pathogenesis of acute myocarditis. The imbalance between the occurrence of reactive oxygen species and the cellular antioxidant defense mechanism plays a key role in myocardial injury of viral myocarditis. Carvedilol, a nonselective beta-adrenoceptor antagonist with addition...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.04.037
更新日期：2010-08-25 00:00:00
abstract：:The present study investigated the mechanisms involved in the antinociception produced by the triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL administered by intra-gastric (i.g.) gavage inhibited glutamate-induced nociception with an ID(50) of 19.0 (13.2-27.5) mg/kg. This action started 60 min (in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.11.028
更新日期：2011-02-25 00:00:00
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journal_title：European journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/0014-2999(93)90356-m
更新日期：1993-03-16 00:00:00
abstract：:Behavioural evidence has accumulated that supports the hypothesis that specific territories of the striatum contribute differentially to the control of motor behaviours. The present experiments compare the behavioural effects of microinjections of amphetamine (20 microg/0.5 microl) with those elicited by the D2-class ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00752-3
更新日期：1998-12-04 00:00:00
abstract：:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Despite the impact of this pathology in the population, nowadays there is no specific treatment for this disease, focusing its treatment on risks factors. However, it is imperative the existence of a specific treatment, due to this...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172699
更新日期：2019-11-15 00:00:00
abstract：:In rat stomach fundus, contractions induced by Ca2+ (1.8 mM) were strikingly potentiated by thapsigargin. This potentiation was partially inhibited by the blockers of Ca2+ release activated channels (CRACs), miconazole and SK&F96365 ([1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole, HCL]) and sli...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01537-9
更新日期：1998-01-19 00:00:00
abstract：:Oral pretreatment with E3330, a novel quinone derivative, attenuated liver injury induced with tumor necrosis factor-alpha in galactosamine-sensitized mice. Tumor necrosis factor-alpha is known to induce inflammatory mediators such as leukotrienes and prostanoids. An in vitro study showed that E3330 inhibited the gene...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90286-d
更新日期：1992-12-08 00:00:00
abstract：:(5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3 .2.1]octane (PTAC) is a potent muscarinic receptor ligand with high affinity for central muscarinic receptors and no or substantially less affinity for a large number of other receptors or binding sites including dopamine receptors. The ligand exhibits parti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00487-7
更新日期：1998-09-04 00:00:00
abstract：:Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine admi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.04.052
更新日期：2006-08-07 00:00:00
abstract：:Loss of beta cells is a pathogenic cause for the development of type 2 diabetes. High glucose/free fatty acid (HG/FFA)-induced glucolipotoxicity was thought to play a role in the beta cell loss. Thus, application of small molecules capable of preventing HG/FFA-induced glucolipotoxicty to beta cells could be an avenue ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.09.023
更新日期：2012-12-05 00:00:00
abstract：:Induction of anaphylactic shock in mice by i.v. antigen challenge (bovine serum albumin, 100 micrograms) or i.v. treatment with the mast cell degranulator compound 48/80 resulted in 80 and 90% mortality rate, respectively. Inhibition of nitric oxide (NO) synthesis from L-arginine by co-injection of the L-arginine anal...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90800-6
更新日期：1991-10-02 00:00:00
abstract：:Pristinamycin IA is a cyclo-peptidic macrolactone antibiotic belonging to the streptogramin family. In the present work, the interaction of pristinamycin IA with the multidrug transporter P-glycoprotein was investigated in the differentiated human intestinal epithelial cell line Caco-2. Pristinamycin IA specifically i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90193-0
更新日期：1995-01-16 00:00:00
abstract：:In order to investigate the possible role of the N-methyl-D-aspartate (NMDA) receptor in the development of the behavioural recovery which occurs following unilateral labyrinthectomy (vestibular compensation) in the guinea pig, we administered systemically the specific NMDA receptor/channel antagonists MK801 and CPP (...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90320-8
更新日期：1989-12-19 00:00:00
