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Pesquisa : D03.383.621.620 [Categoria DeCS]
Referências encontradas : 153 [refinar]
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[PMID]:28618969
[Au] Autor:Ranjan A; German N; Mikelis C; Srivenugopal K; Srivastava SK
[Ad] Endereço:1 Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
[Ti] Título:Penfluridol induces endoplasmic reticulum stress leading to autophagy in pancreatic cancer.
[So] Source:Tumour Biol;39(6):1010428317705517, 2017 Jun.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression. In this study, we demonstrated that penfluridol induced endoplasmic reticulum stress in BxPC-3, AsPC-1, and Panc-1 pancreatic cancer cell lines as indicated by upregulation of endoplasmic reticulum stress markers such as binding protein (BIP), C/EBP homologous protein (CHOP) and inositol requiring 1α (IRE1α) after treatment with penfluridol in a concentration-dependent manner. Inhibiting endoplasmic reticulum stress by pretreatment with pharmacological inhibitors such as sodium phenylbutyrate and mithramycin or by silencing CHOP using CHOP small interfering RNA, blocked penfluridol-induced autophagy. These results clearly indicate that penfluridol-induced endoplasmic reticulum stress lead to autophagy in our model. Western blot analysis of subcutaneously implanted AsPC-1 and BxPC-3 tumors as well as orthotopically implanted Panc-1 tumors demonstrated upregulation of BIP, CHOP, and IRE1α expression in the tumor lysates from penfluridol-treated mice as compared to tumors from control mice. Altogether, our study establishes that penfluridol-induced endoplasmic reticulum stress leads to autophagy resulting in reduced pancreatic tumor growth. Our study opens a new therapeutic target for advanced chemotherapies against pancreatic cancer.
[Mh] Termos MeSH primário: Endorribonucleases/biossíntese
Proteínas de Choque Térmico/genética
Neoplasias Pancreáticas/tratamento farmacológico
Penfluridol/administração & dosagem
Proteínas Serina-Treonina Quinases/biossíntese
Fator de Transcrição CHOP/biossíntese
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Retículo Endoplasmático/efeitos dos fármacos
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Endorribonucleases/genética
Regulação Neoplásica da Expressão Gênica
Proteínas de Choque Térmico/biossíntese
Seres Humanos
Camundongos
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/patologia
Proteínas Serina-Treonina Quinases/genética
RNA Interferente Pequeno/genética
Fator de Transcrição CHOP/antagonistas & inibidores
Fator de Transcrição CHOP/genética
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DDIT3 protein, human); 0 (Heat-Shock Proteins); 0 (RNA, Small Interfering); 0 (molecular chaperone GRP78); 147336-12-7 (Transcription Factor CHOP); 25TLU22Q8H (Penfluridol); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 3.1.- (Endoribonucleases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317705517


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[PMID]:27811009
[Au] Autor:Hedrick E; Li X; Safe S
[Ad] Endereço:Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station, Texas.
[Ti] Título:Penfluridol Represses Integrin Expression in Breast Cancer through Induction of Reactive Oxygen Species and Downregulation of Sp Transcription Factors.
[So] Source:Mol Cancer Ther;16(1):205-216, 2017 Jan.
[Is] ISSN:1538-8514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It was recently demonstrated the penfluridol inhibited breast tumor growth and metastasis and this was associated with downregulation of α6- and ß4-integrins. In this study, we observed the penfluridol induced reactive oxygen species (ROS) and this was the primary mechanism of action. Penfluridol-mediated growth inhibition, induction of apoptosis, and inhibition of breast cancer cell migration was attenuated after cotreatment with glutathione. Penfluridol also downregulated Sp transcription factors Sp1, Sp3, and Sp4 through epigenetic downregulation of cMyc and cMyc-regulated miRNAs (miR27a and miR20a/miR17) and induction of the miR-regulated Sp transcriptional repressors ZBTB10 and ZBTB4. α6- and ß4-integrins as well as α5- and ß1-integrins are Sp-regulated genes that are also coregulated by the orphan nuclear receptor NR4A1 and these integrins can be targeted by agents such as penfluridol that suppress Sp1, Sp3, and Sp4 and also by NR4A1 antagonists. Mol Cancer Ther; 16(1); 205-16. ©2016 AACR.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Integrinas/genética
Penfluridol/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Fatores de Transcrição Sp/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Modelos Animais de Doenças
Feminino
Genes myc
Seres Humanos
MicroRNAs/genética
Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo
Ligação Proteica
Transdução de Sinais/efeitos dos fármacos
Ensaios Antitumorais Modelo de Xenoenxerto
Dedos de Zinco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrins); 0 (MicroRNAs); 0 (NR4A1 protein, human); 0 (Nuclear Receptor Subfamily 4, Group A, Member 1); 0 (Reactive Oxygen Species); 0 (Sp Transcription Factors); 25TLU22Q8H (Penfluridol)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE
[do] DOI:10.1158/1535-7163.MCT-16-0451


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[PMID]:26627008
[Au] Autor:Ranjan A; Gupta P; Srivastava SK
[Ad] Endereço:Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, Texas.
[Ti] Título:Penfluridol: An Antipsychotic Agent Suppresses Metastatic Tumor Growth in Triple-Negative Breast Cancer by Inhibiting Integrin Signaling Axis.
[So] Source:Cancer Res;76(4):877-90, 2016 Feb 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metastasis of breast cancer, especially to the brain, is the major cause of mortality. The inability of anticancer agents to cross the blood-brain-barrier represents a critical challenge for successful treatment. In the current study, we investigated the antimetastatic potential of penfluridol, an antipsychotic drug frequently prescribed for schizophrenia with anticancer activity. We show that penfluridol induced apoptosis and reduced the survival of several metastatic triple-negative breast cancer (TNBC) cell lines. In addition, penfluridol treatment significantly reduced the expression of integrin α6, integrin ß4, Fak, paxillin, Rac1/2/3, and ROCK1 in vitro. We further evaluated the efficacy of penfluridol in three different in vivo tumor models. We demonstrate that penfluridol administration to an orthotopic model of breast cancer suppressed tumor growth by 49%. On the other hand, penfluridol treatment inhibited the growth of metastatic brain tumors introduced by intracardiac or intracranial injection of breast cancer cells by 90% and 72%, respectively. Penfluridol-treated tumors from all three models exhibited reduced integrin ß4 and increased apoptosis. Moreover, chronic administration of penfluridol failed to elicit significant toxic or behavioral side effects in mice. Taken together, our results indicate that penfluridol effectively reduces the growth of primary TNBC tumors and especially metastatic growth in the brain by inhibiting integrin signaling, and prompt further preclinical investigation into repurposing penfluridol for the treatment of metastatic TNBC.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Penfluridol/uso terapêutico
Neoplasias de Mama Triplo Negativas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antipsicóticos/administração & dosagem
Linhagem Celular Tumoral
Feminino
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Penfluridol/administração & dosagem
Transdução de Sinais
Neoplasias de Mama Triplo Negativas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antipsychotic Agents); 25TLU22Q8H (Penfluridol)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151203
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-15-1233


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[PMID]:25788571
[Au] Autor:Enyeart JJ; Enyeart JA
[Ad] Endereço:Department of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, Ohio enyeart.1@osu.edu.
[Ti] Título:Adrenal fasciculata cells express T-type and rapidly and slowly activating L-type Ca2+ channels that regulate cortisol secretion.
[So] Source:Am J Physiol Cell Physiol;308(11):C899-918, 2015 Jun 01.
[Is] ISSN:1522-1563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In whole cell patch-clamp recordings, we characterized the L-type Ca(2+) currents in bovine adrenal zona fasciculata (AZF) cells and explored their role, along with the role of T-type channels, in ACTH- and angiotensin II (ANG II)-stimulated cortisol secretion. Two distinct dihydropyridine-sensitive L-type currents were identified, both of which were activated at relatively hyperpolarized potentials. One activated with rapid kinetics and, in conjunction with Northern blotting and PCR, was determined to be Cav1.3. The other, expressed in approximately one-half of AZF cells, activated with extremely slow voltage-dependent kinetics and combined properties not previously reported for an L-type Ca(2+) channel. The T-type Ca(2+) channel antagonist 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2) inhibited Cav3.2 current in these cells, as well as ACTH- and ANG II-stimulated cortisol secretion, at concentrations that did not affect L-type currents. In contrast, nifedipine specifically inhibited L-type currents and cortisol secretion, but less effectively than TTA-P2. Diphenylbutylpiperidine Ca(2+) antagonists, including pimozide, penfluridol, and fluspirilene, and the dihydropyridine niguldipine blocked Cav3.2 and L-type currents and inhibited ACTH-stimulated cortisol secretion with similar potency. This study shows that bovine AZF cells express three Ca(2+) channels, the voltage-dependent gating and kinetics of which could orchestrate complex mechanisms linking peptide hormone receptors to cortisol secretion through action potentials or sustained depolarization. The function of the novel, slowly activating L-type channel is of particular interest in this respect. Regardless, the well-correlated selective inhibition of T- and L-type currents and ACTH- and ANG II-stimulated cortisol secretion by TTA-P2 and nifedipine establish the critical importance of these channels in AZF cell physiology.
[Mh] Termos MeSH primário: Potenciais de Ação/efeitos dos fármacos
Canais de Cálcio Tipo L/genética
Canais de Cálcio Tipo T/genética
Cálcio/metabolismo
Hidrocortisona/secreção
Zona Fasciculada/metabolismo
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/farmacologia
Angiotensina II/farmacologia
Animais
Benzamidas/farmacologia
Bloqueadores dos Canais de Cálcio/farmacologia
Canais de Cálcio Tipo L/metabolismo
Canais de Cálcio Tipo T/metabolismo
Bovinos
AMP Cíclico/farmacologia
Di-Hidropiridinas/farmacologia
Fluspirileno/farmacologia
Expressão Gênica
Microeletrodos
Nifedipino/farmacologia
Técnicas de Patch-Clamp
Penfluridol/farmacologia
Pimozida/farmacologia
Piperidinas/farmacologia
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Análise de Célula Única
Zona Fasciculada/citologia
Zona Fasciculada/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (3,5-dichloro-N-(1-(2,2-dimethyltetrahydropyran-4-ylmethyl)-4-fluoropiperidin-4-ylmethyl)benzamide); 0 (Benzamides); 0 (Calcium Channel Blockers); 0 (Calcium Channels, L-Type); 0 (Calcium Channels, T-Type); 0 (Dihydropyridines); 0 (Piperidines); 0 (Protein Isoforms); 11128-99-7 (Angiotensin II); 1HIZ4DL86F (Pimozide); 25TLU22Q8H (Penfluridol); 9002-60-2 (Adrenocorticotropic Hormone); C5QA4GLR9M (Fluspirilene); E0399OZS9N (Cyclic AMP); I9ZF7L6G2L (Nifedipine); SY7Q814VUP (Calcium); WI4X0X7BPJ (Hydrocortisone); Z81N45O25Z (niguldipine)
[Em] Mês de entrada:1508
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150320
[St] Status:MEDLINE
[do] DOI:10.1152/ajpcell.00002.2015


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[PMID]:25637283
[Au] Autor:Chien W; Sun QY; Lee KL; Ding LW; Wuensche P; Torres-Fernandez LA; Tan SZ; Tokatly I; Zaiden N; Poellinger L; Mori S; Yang H; Tyner JW; Koeffler HP
[Ad] Endereço:Cancer Science Institute of Singapore, National University of Singapore, Singapore. Electronic address: csicw@nus.edu.sg.
[Ti] Título:Activation of protein phosphatase 2A tumor suppressor as potential treatment of pancreatic cancer.
[So] Source:Mol Oncol;9(4):889-905, 2015 Apr.
[Is] ISSN:1878-0261
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We utilized three tiers of screening to identify novel therapeutic agents for pancreatic cancers. First, we analyzed 14 pancreatic cancer cell lines against a panel of 66 small-molecule kinase inhibitors and dasatinib was the most potent. Second, we performed RNA expression analysis on 3 dasatinib-resistant and 3 dasatinib-sensitive pancreatic cancer cell lines to profile their gene expression. Third, gene profiling data was integrated with the Connectivity Map database to search for potential drugs. Thioridazine was one of the top ranking small molecules with highly negative enrichment. Thioridazine and its family members of phenothiazine including penfluridol caused pancreatic cancer cell death and affected protein expression levels of molecules involved in cell cycle regulation, apoptosis, and multiple kinase activities. This family of drugs causes activation of protein phosphatase 2 (PP2A). The drug FTY-720 (activator of PP2A) induced apoptosis of pancreatic cancer cells. Silencing catalytic unit of PP2A rendered pancreatic cancer cells resistant to penfluridol. Our observations suggest potential therapeutic use of penfluridol or similar agent associated with activation of PP2A in pancreatic cancers.
[Mh] Termos MeSH primário: Neoplasias Pancreáticas/tratamento farmacológico
Neoplasias Pancreáticas/enzimologia
Proteína Fosfatase 2/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Simulação por Computador
Dasatinibe/farmacologia
Avaliação Pré-Clínica de Medicamentos
Ativação Enzimática/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Neoplasias Pancreáticas/genética
Penfluridol/farmacologia
Penfluridol/uso terapêutico
Fenotiazinas/farmacologia
Inibidores de Proteínas Quinases/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Phenothiazines); 0 (Protein Kinase Inhibitors); 0 (Tumor Suppressor Proteins); 25TLU22Q8H (Penfluridol); EC 3.1.3.16 (Protein Phosphatase 2); GS9EX7QNU6 (phenothiazine); RBZ1571X5H (Dasatinib)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150201
[St] Status:MEDLINE


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[PMID]:24528079
[Au] Autor:Wu L; Liu YY; Li ZX; Zhao Q; Wang X; Yu Y; Wang YY; Wang YQ; Luo F
[Ad] Endereço:Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China E-mail : luofeng@medmail.com.cn.
[Ti] Título:Anti-tumor effects of penfluridol through dysregulation of cholesterol homeostasis.
[So] Source:Asian Pac J Cancer Prev;15(1):489-94, 2014.
[Is] ISSN:2476-762X
[Cp] País de publicação:Thailand
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. METHODS: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p- aminophenazone (CHOD-PAP) method. RESULTS: Penfluridol inhibited the proliferation of B16 melanoma (B16/ F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. CONCLUSION: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Colesterol/metabolismo
Neoplasias do Colo/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Melanoma Experimental/tratamento farmacológico
Penfluridol/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Antipsicóticos/farmacologia
Neoplasias da Mama/metabolismo
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Colesterol/sangue
Neoplasias do Colo/metabolismo
Feminino
Homeostase/efeitos dos fármacos
Neoplasias Pulmonares/metabolismo
Melanoma Experimental/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Penfluridol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 25TLU22Q8H (Penfluridol); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:170308
[Lr] Data última revisão:
170308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140218
[St] Status:MEDLINE


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[PMID]:24402080
[Au] Autor:Lu L; Wang W; Peng Y; Li J; Wang L; Wang X
[Ad] Endereço:State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Xicheng District, Beijing, 100050, China.
[Ti] Título:Electrophysiology and pharmacology of tandem domain potassium channel TREK-1 related BDNF synthesis in rat astrocytes.
[So] Source:Naunyn Schmiedebergs Arch Pharmacol;387(4):303-12, 2014 Apr.
[Is] ISSN:1432-1912
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In the present study, the functional properties and pharmacology of two-pore domain potassium channel (K2P) TREK-1 in primary cultured rat brain astrocytes were investigated. Western blot, patch clamping techniques, and ELISA were used to detect the distribution and function of TREK-1 as well as the expression of brain-derived neurotrophic factor (BDNF) on the primary cultured astrocytes. It was shown that TREK-1 protein expressed in astrocytes was 2.4-fold higher than it was expressed in microglia. Single channel recording via patch clamping showed that the TREK-1 outward currents in astrocytes could be activated by arachidonic acid (AA) or chloroform with the conductance of 113 ± 14 and 120 ± 13 pS, respectively. The current was also sensitive to mechanical stretch and intracellular acidification. Negative pressure (-30 cm H2O) and acidification of intracellular solution (pH 6.8 or 6.3) both enhanced TREK-1 channel open probability significantly. Further pharmacological studies showed that TREK-1 antagonist penfluridol inhibited AA-induced currents, and both penfluridol and methionine (TREK-1 blockers) significantly increased BDNF level in astrocytes by 50 %. These results indicated that TREK-1 channel current was a major component of K2P currents in astrocytes. TREK-1 channels might play important roles in regulating the function of astrocytes and might be used as a drug target for neuroprotection.
[Mh] Termos MeSH primário: Astrócitos/fisiologia
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Microglia/fisiologia
Canais de Potássio de Domínios Poros em Tandem/fisiologia
[Mh] Termos MeSH secundário: Animais
Ácido Araquidônico/farmacologia
Células Cultivadas
Clorofórmio/farmacologia
Penfluridol
Canais de Potássio de Domínios Poros em Tandem/agonistas
Canais de Potássio de Domínios Poros em Tandem/antagonistas & inibidores
Ratos
Ratos Wistar
Estresse Mecânico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Potassium Channels, Tandem Pore Domain); 0 (potassium channel protein TREK-1); 25TLU22Q8H (Penfluridol); 27YG812J1I (Arachidonic Acid); 7V31YC746X (Chloroform)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140110
[St] Status:MEDLINE
[do] DOI:10.1007/s00210-013-0952-2


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[PMID]:21613605
[Au] Autor:Enyeart JJ; Liu H; Enyeart JA
[Ad] Endereço:Department of Neuroscience, The Ohio State University, College of Medicine and Public Health, Columbus, 43210-1239, USA. enyeart.1@osu.edu
[Ti] Título:Calcium-dependent inhibition of adrenal TREK-1 channels by angiotensin II and ionomycin.
[So] Source:Am J Physiol Cell Physiol;301(3):C619-29, 2011 Sep.
[Is] ISSN:1522-1563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bovine adrenocortical cells express bTREK-1 K(+) (bovine KCNK2) channels that are inhibited by ANG II through a Gq-coupled receptor by separate Ca(2+) and ATP hydrolysis-dependent signaling pathways. Whole cell and single patch clamp recording from adrenal zona fasciculata (AZF) cells were used to characterize Ca(2+)-dependent inhibition of bTREK-1. In whole cell recordings with pipette solutions containing 0.5 mM EGTA and no ATP, the Ca(2+) ionophore ionomycin (1 µM) produced a transient inhibition of bTREK-1 that reversed spontaneously within minutes. At higher concentrations, ionomycin (5-10 µM) produced a sustained inhibition of bTREK-1 that was reversible upon washing, even in the absence of hydrolyzable [ATP](i). BAPTA was much more effective than EGTA at suppressing bTREK-1 inhibition by ANG II. When intracellular Ca(2+) concentration ([Ca(2+)](i)) was buffered to 20 nM with either 11 mM BAPTA or EGTA, ANG II (10 nM) inhibited bTREK-1 by 12.0 ± 4.5% (n=11) and 59.3 ± 8.4% (n=4), respectively. Inclusion of the water-soluble phosphatidylinositol 4,5-bisphosphate (PIP(2)) analog DiC(8)PI(4,5)P(2) in the pipette failed to increase bTREK-1 expression or reduce its inhibition by ANG II. The open probability (P(o)) of unitary bTREK-1 channels recorded from inside-out patches was reduced by Ca(2+) (10-35 µM) in a concentration-dependent manner. These results are consistent with a model in which ANG II inhibits bTREK-1 K(+) channels by a Ca(2+)-dependent mechanism that does not require the depletion of membrane-associated PIP(2). They further indicate that the Ca(2+) source is located in close proximity within a "Ca(2+) nanodomain" of bTREK-1 channels, where [Ca(2+)](i) may reach concentrations of >10 µM. bTREK-1 is the first two-pore K(+) channel shown to be inhibited by Ca(2+) through activation of a G protein-coupled receptor.
[Mh] Termos MeSH primário: Córtex Suprarrenal/citologia
Angiotensina II/farmacologia
Sinalização do Cálcio/fisiologia
Ativação do Canal Iônico/fisiologia
Ionomicina/farmacologia
Canais de Potássio de Domínios Poros em Tandem/metabolismo
[Mh] Termos MeSH secundário: Adenilil Imidodifosfato/farmacologia
Animais
Tampões (Química)
Cálcio/metabolismo
Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Bovinos
Células Cultivadas
Ácido Egtázico/análogos & derivados
Ácido Egtázico/metabolismo
Ácido Egtázico/farmacologia
Estimulação Elétrica
Fenômenos Eletrofisiológicos/efeitos dos fármacos
Fenômenos Eletrofisiológicos/fisiologia
Ativação do Canal Iônico/efeitos dos fármacos
Masculino
Técnicas de Patch-Clamp
Penfluridol/farmacologia
Fosfatidilinositol 4,5-Difosfato/análogos & derivados
Fosfatidilinositol 4,5-Difosfato/antagonistas & inibidores
Fosfatidilinositol 4,5-Difosfato/metabolismo
Canais de Potássio de Domínios Poros em Tandem/antagonistas & inibidores
Uridina Trifosfato/metabolismo
Uridina Trifosfato/farmacologia
Zona Fasciculada/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Buffers); 0 (Phosphatidylinositol 4,5-Diphosphate); 0 (Potassium Channels, Tandem Pore Domain); 0 (potassium channel protein TREK-1); 11128-99-7 (Angiotensin II); 25612-73-1 (Adenylyl Imidodiphosphate); 25TLU22Q8H (Penfluridol); 526U7A2651 (Egtazic Acid); 56092-81-0 (Ionomycin); K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid); SY7Q814VUP (Calcium); UT0S826Z60 (Uridine Triphosphate)
[Em] Mês de entrada:1201
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110527
[St] Status:MEDLINE
[do] DOI:10.1152/ajpcell.00117.2011


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[PMID]:16625563
[Au] Autor:Soares BG; Lima MS
[Ad] Endereço:Brazilian Cochrane Centre, Rua Pedro de Toledo 598, Vila Clementino, São Paulo, SP, Brazil, 04039-001. bgos@terra.com.br
[Ti] Título:Penfluridol for schizophrenia.
[So] Source:Cochrane Database Syst Rev;(2):CD002923, 2006 Apr 19.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Penfluridol, available since 1970, is an unusual long acting oral antipsychotic agent for the treatment of schizophrenia. It may be considered a depot medication as it is administered once a week. OBJECTIVES: To review the effects of penfluridol for treatment of those with schizophrenia and schizophrenia-like illnesses in comparison to placebo, other antipsychotic medication or no intervention. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's Register (2005), the Cochrane Central Register of Controlled Trials (2003-5) and LILACS (1982-2005). We hand searched references of all identified studies and sought citations of these studies in the Science Citation Index. We contacted the authors of trials and the manufacturer of penfluridol. SELECTION CRITERIA: We reliably selected all randomised clinical trials comparing penfluridol to placebo or typical or atypical antipsychotic drugs for schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS: We independently extracted and analysed data on an intention-to-treat basis. We calculated the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and where possible calculated the number needed to treat. We calculated weighted mean differences (WMD) for continuous data. MAIN RESULTS: We included twenty-five studies with a total of 1024 participants. Most of these studies were undertaken in the 1970s when penfluridol was launched. Ten studies, with 365 patients, compared penfluridol to placebo. In the meta-analysis of medium-term lasting studies, penfluridol was superior to placebo in the main efficacy measures: 'improvement in global state' (n=159, 4 RCTs, RR 0.69 CI 0.6 to 0.8, NNT 3 CI 2 to 10) and 'needing additional antipsychotic' (n=138, 5 RCTs, RR 0.43 CI 0.2 to 0.8, NNT 3 CI 1.8 to 20).A total of 449 patients from eleven studies were randomised to penfluridol or oral typical antipsychotics. There were no particular differences between penfluridol versus chlorpromazine, fluphenazine, trifluoperazine, thioridazine, or thiothixene for the main outcome measures in medium-term trials: 'improvement on global state' (N=2 studies), 'leaving the study early' (N=6), 'needing additional antipsychotic' (N=3), needing antiparkinsonian medication (N=2), and side-effects. Six studies, with 274 patients, compared penfluridol to depot typical antipsychotics. In general, for the efficacy and safety measures, no differences were established, but penfluridol was superior in keeping the patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to 0.97, NNT 6 CI 3.4 to 50). AUTHORS' CONCLUSIONS: Although there are shortcomings and gaps in the data, there appears to be enough overall consistency for different outcomes. The efficacy and adverse effects profile of penfluridol are similar to other typical antipsychotics; both oral and depot. Furthermore, penfluridol is shown to be an adequate treatment option for people with schizophrenia, especially those who do not respond to oral medication on a daily basis and do not adapt well to depot drugs. One of the results favouring penfluridol was a lower drop out rate in medium term when compared to depot medications. It is also an option for chronic sufferers of schizophrenia with residual psychotic symptoms who nevertheless need continuous use of antipsychotic medication. An additional benefit of penfluridol is that it is a low-cost intervention.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Penfluridol/uso terapêutico
Esquizofrenia/tratamento farmacológico
[Mh] Termos MeSH secundário: Antipsicóticos/efeitos adversos
Seres Humanos
Penfluridol/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 25TLU22Q8H (Penfluridol)
[Em] Mês de entrada:0606
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060421
[St] Status:MEDLINE


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[PMID]:16018933
[Au] Autor:Kalaitzi CK; Sakkas D
[Ti] Título:Brief psychotic disorder associated with Sturge-Weber syndrome.
[So] Source:Eur Psychiatry;20(4):356-7, 2005 Jun.
[Is] ISSN:0924-9338
[Cp] País de publicação:France
[La] Idioma:eng
[Mh] Termos MeSH primário: Transtornos Psicóticos/complicações
Síndrome de Sturge-Weber/complicações
[Mh] Termos MeSH secundário: Adulto
Antipsicóticos/uso terapêutico
Comorbidade
Seres Humanos
Deficiência Intelectual/complicações
Deficiência Intelectual/diagnóstico
Masculino
Penfluridol/uso terapêutico
Transtornos Psicóticos/diagnóstico
Transtornos Psicóticos/tratamento farmacológico
Recidiva
Síndrome de Sturge-Weber/diagnóstico
[Pt] Tipo de publicação:CASE REPORTS; LETTER
[Nm] Nome de substância:
0 (Antipsychotic Agents); 25TLU22Q8H (Penfluridol)
[Em] Mês de entrada:0601
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:050716
[St] Status:MEDLINE



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