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[PMID]:28291959
[Au] Autor:Liang W; Chen M; Zheng D; Li J; Song M; Zhang W; Feng J; Lan J
[Ti] Título:The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway.
[So] Source:Cell Physiol Biochem;41(3):1020-1034, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. METHODS: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. RESULTS: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. CONCLUSION: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Glucose/toxicidade
Miócitos Cardíacos/efeitos dos fármacos
Canais de Potássio/genética
Espécies Reativas de Oxigênio/antagonistas & inibidores
Receptor 4 Toll-Like/genética
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Animais
Linhagem Celular
Ácidos Decanoicos/farmacologia
Diazóxido/farmacologia
Regulação da Expressão Gênica
Glibureto/farmacologia
Hidroxiácidos/farmacologia
Imidazóis/farmacologia
Indóis/farmacologia
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Miócitos Cardíacos/citologia
Miócitos Cardíacos/metabolismo
Necrose/genética
Necrose/metabolismo
Necrose/prevenção & controle
Estresse Oxidativo
Pinacidil/farmacologia
Canais de Potássio/agonistas
Canais de Potássio/metabolismo
Ratos
Espécies Reativas de Oxigênio/metabolismo
Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores
Proteína Serina-Treonina Quinases de Interação com Receptores/genética
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Transdução de Sinais
Sulfonamidas/farmacologia
Receptor 4 Toll-Like/antagonistas & inibidores
Receptor 4 Toll-Like/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Decanoic Acids); 0 (Hydroxy Acids); 0 (Imidazoles); 0 (Indoles); 0 (Potassium Channels); 0 (Reactive Oxygen Species); 0 (Sulfonamides); 0 (Tlr4 protein, rat); 0 (Toll-Like Receptor 4); 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate); 0 (mitochondrial K(ATP) channel); 0 (necrostatin-1); 624-00-0 (5-hydroxydecanoic acid); 7B0ZZH8P2W (Pinacidil); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 2.7.11.1 (receptor-interacting protein 3, rat); IY9XDZ35W2 (Glucose); O5CB12L4FN (Diazoxide); SX6K58TVWC (Glyburide); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1159/000461391


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[PMID]:28270043
[Au] Autor:Li S; Lei Y; Chen JD
[Ad] Endereço:a Veterans Research and Education Foundation, VA Medical Center , Oklahoma City , OK , USA.
[Ti] Título:Roles of ATP sensitive potassium channel in modulating gastric tone and accommodation in dogs.
[So] Source:Scand J Gastroenterol;52(5):515-522, 2017 May.
[Is] ISSN:1502-7708
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The ATP sensitive potassium (K ) channel plays an important role in the regulation of resting membrane potential and membrane excitability. The role of the K channel in modulating gastric motility is unclear. The aim of this study was to investigate the role and mechanism of the K channel in modulating gastric tone and accommodation in dogs. MATERIALS AND METHODS: Gastric volume under a constant pressure reflecting gastric tone was measured using a barostat device in dogs equipped with a gastric cannula. Gastric accommodation was evaluated by the difference in gastric volume before and after a liquid meal. The roles of cholinergic and nitrergic pathways in the inhibitory effect of pinacidil (a K opener) were assessed. RESULTS: 1) Pinacidil dose-dependently decreased gastric tone at a dosage of 30 (p = 0.628), 100 (p = 0.013) and 300 µg kg (p < 0.001). 2) Glibenclamide, a K blocker, completely blocked the inhibitory effect of pinacidil on gastric tone. 3) Atropine did not block the inhibitory effect of pinacidil on gastric tone but N -Nitro-L-arginine methyl ester markedly attenuated the inhibitory effect of pinacidil (p = 0.004). 4) Glibenclamide significantly reduced gastric accommodation (p < 0.001) while pinacidil had no effects on gastric accommodation. 5) Glibenclamide significantly reduced nitric oxide donor sodium nitroprusside-induced gastric relaxation. CONCLUSIONS: These findings indicate that the K channel plays an important role in modulating gastric tone and accommodation in dogs. The inhibitory effect of pinacidil on gastric tone was through the nitrergic pathway as well as acting directly on smooth muscle cells.
[Mh] Termos MeSH primário: Motilidade Gastrointestinal/efeitos dos fármacos
Glibureto/administração & dosagem
Canais KATP/fisiologia
Pinacidil/administração & dosagem
Estômago/fisiologia
[Mh] Termos MeSH secundário: Animais
Cães
Feminino
Canais KATP/antagonistas & inibidores
Miócitos de Músculo Liso/efeitos dos fármacos
Vasodilatação/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KATP Channels); 7B0ZZH8P2W (Pinacidil); SX6K58TVWC (Glyburide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1080/00365521.2017.1289238


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[PMID]:27693800
[Au] Autor:Mori K; Yamashita Y; Teramoto N
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine, Saga University, Saga 849-8501, Japan; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
[Ti] Título:Effects of ZD0947, a novel and potent ATP-sensitive K channel opener, on smooth muscle-type ATP-sensitive K channels.
[So] Source:Eur J Pharmacol;791:773-779, 2016 Nov 15.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The effects of ZD0947, a novel ATP-sensitive K channel (K channel) opener, on the activity of reconstituted K channels were investigated using cell-attached recordings. K channels were studied in HEK 293 cells by co-expression of inwardly rectifying-6 family K channel subunits (Kir6.x: Kir6.1 and Kir6.2) with 3 different types of sulphonylurea receptors (SUR.x: SUR1, SUR2A and SUR2B). ZD0947 (100µM) activated SUR2B/Kir6.2 channels in a concentration-dependent manner, but caused only weak activation of SUR1/Kir6.2 channels and SUR2A/Kir6.2 channels expressed in HEK 293 cells. ZD0947 reversibly suppressed diazoxide-elicited SUR1/Kir6.2 channels activity and pinacidil-elicited SUR2A/Kir6.2 channel activity. However, ZD0947 did not affect SUR2B/Kir6.2 channels fully activated by 100µM pinacidil. ZD0947 had little inhibitory effects on the activity of Kir6.2ΔC26 channels (a truncated isoform of Kir6.2) or its mutant channels (i.e. Kir6.2ΔC26C166A) expressed in HEK 293 cells. ZD0947 also elicited activity in SUR2B/Kir6.1 channels expressed in HEK 293 cells, in a concentration-dependent manner. Therefore, ZD0947 is a relatively effective activator of smooth muscle-type K channels (SUR2B/Kir6.1 and SUR2B/Kir6.2) but is a partial antagonist of pancreatic-type K channels (i.e. SUR1/Kir6.2) and cardiac-type K channels (i.e. SUR2A/Kir6.2). These results suggest that a pharmacological agent can possess either agonist or antagonist actions on the activity of K channels, depending on the subtype of SUR.x.
[Mh] Termos MeSH primário: Di-Hidropiridinas/farmacologia
Ativação do Canal Iônico/efeitos dos fármacos
Canais KATP/química
Canais KATP/metabolismo
Músculo Liso/metabolismo
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
Pinacidil/farmacologia
Receptores Sulfonilureia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dihydropyridines); 0 (KATP Channels); 0 (Sulfonylurea Receptors); 0 (ZD0947); 7B0ZZH8P2W (Pinacidil)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE


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[PMID]:27562702
[Au] Autor:Shimbo T; Adachi T; Fujisawa S; Hongoh M; Ohba T; Ono K
[Ad] Endereço:Department of Cell Physiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
[Ti] Título:In vitro effect of nicorandil on the carbachol-induced contraction of the lower esophageal sphincter of the rat.
[So] Source:J Pharmacol Sci;131(4):267-74, 2016 Aug.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The lower esophageal sphincter (LES) is a specialized region of the esophageal smooth muscle that allows the passage of a swallowed bolus into the stomach. Nitric oxide (NO) plays a major role in LES relaxation. Nicorandil possesses dual properties of a NO donor and an ATP-sensitive potassium channel (KATP channel) agonist, and is expected to reduce LES tone. This study investigated the mechanisms underlying the effects of nicorandil on the LES. Rat LES tissues were placed in an organ bath, and activities were recorded using an isometric force transducer. Carbachol-induced LES contraction was significantly inhibited by KATP channel agonists in a concentration-dependent manner; pinacidil >> nicorandil ≈ diazoxide. Nicorandil-induced relaxation of the LES was prevented by pretreatment with glibenclamide, whereas N(G)-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin were ineffective at preventing nicorandil-induced LES relaxation. Furthermore, nicorandil did not affect high K(+)-induced LES contraction. Reverse-transcription polymerase chain reaction analysis and immunohistochemistry revealed expression of KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1) and ABCC9 (SUR2) subunits of the KATP channel in the rat lower esophagus. These findings indicate that nicorandil causes LES relaxation chiefly by activating the KATP channel, and that it may provide an additional pharmacological tool for the treatment of spastic esophageal motility disorders.
[Mh] Termos MeSH primário: Carbacol/farmacologia
Esfíncter Esofágico Inferior/efeitos dos fármacos
Contração Muscular/efeitos dos fármacos
Nicorandil/farmacologia
[Mh] Termos MeSH secundário: Animais
Diazóxido/farmacologia
Relação Dose-Resposta a Droga
Glibureto/farmacologia
Técnicas In Vitro
Canais KATP/agonistas
Canais KATP/biossíntese
NG-Nitroarginina Metil Éster/farmacologia
Oxidiazóis/farmacologia
Peptídeos/farmacologia
Pinacidil/farmacologia
Potássio/farmacologia
Quinoxalinas/farmacologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one); 0 (KATP Channels); 0 (Oxadiazoles); 0 (Peptides); 0 (Quinoxalines); 260456HAM0 (Nicorandil); 773HER9B6T (iberiotoxin); 7B0ZZH8P2W (Pinacidil); 8Y164V895Y (Carbachol); O5CB12L4FN (Diazoxide); RWP5GA015D (Potassium); SX6K58TVWC (Glyburide); V55S2QJN2X (NG-Nitroarginine Methyl Ester)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160827
[St] Status:MEDLINE


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[PMID]:27283775
[Au] Autor:Frommeyer G; Ellermann C; Dechering DG; Kochhäuser S; Bögeholz N; Güner F; Leitz P; Pott C; Eckardt L
[Ad] Endereço:Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany. gerrit.frommeyer@ukmuenster.de.
[Ti] Título:Ranolazine and Vernakalant Prevent Ventricular Arrhythmias in an Experimental Whole-Heart Model of Short QT Syndrome.
[So] Source:J Cardiovasc Electrophysiol;27(10):1214-1219, 2016 Oct.
[Is] ISSN:1540-8167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ranolazine has been reported to have an antiarrhythmic potential. The aim of this study was to assess the electrophysiologic effects of ranolazine and to compare its effects to vernakalant in an experimental whole-heart model of short-QT syndrome. METHODS: Rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK channel opener, was administered (1 µM). RESULTS: Endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (- 34 milliseconds, P < 0.05) and action potential duration (APD ; - 31 milliseconds, P < 0.05). This was accompanied by a reduction of effective refractory period (ERP; - 32 milliseconds, P < 0.05). Subsequently, hearts were additionally perfused with ranolazine (10 µM, n = 12) or vernakalant (10 µM, n = 14). Ranolazine led to an increase of QT-interval (+ 29 milliseconds, P < 0.05), APD (+ 18 milliseconds, P < 0.05) and ERP (+ 28 milliseconds, P < 0.05) as compared with sole pinacidil treatment. Similar results were observed under the influence of vernakalant (APD90: + 25 milliseconds, QT-interval: + 34 milliseconds, ERP: + 31 milliseconds). Under the influence of pinacidil, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and aggressive burst stimulation in 8 of 12 hearts (ranolazine group, 34 episodes) and 7 of 14 hearts (vernakalant group, 24 episodes). Additional infusion of ranolazine (1 of 12 hearts, 1 episode) or vernakalant (1 of 14 hearts, 3 episodes) led to a significant suppression of VF. CONCLUSION: In the present pharmacologic model of short QT syndrome treatment with pinacidil led to an increased inducibility of VF in association with a reduction in ERP. Additional treatment with ranolazine or vernakalant reversed this effect and demonstrated potent antiarrhythmic properties based on an increase of ERP.
[Mh] Termos MeSH primário: Anisóis/farmacologia
Antiarrítmicos/farmacologia
Arritmias Cardíacas/tratamento farmacológico
Pirrolidinas/farmacologia
Ranolazina/farmacologia
Bloqueadores dos Canais de Sódio/farmacologia
Fibrilação Ventricular/prevenção & controle
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Arritmias Cardíacas/diagnóstico
Arritmias Cardíacas/fisiopatologia
Estimulação Cardíaca Artificial
Modelos Animais de Doenças
Eletrocardiografia
Frequência Cardíaca/efeitos dos fármacos
Preparação de Coração Isolado
Pinacidil
Coelhos
Fatores de Tempo
Fibrilação Ventricular/diagnóstico
Fibrilação Ventricular/fisiopatologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anisoles); 0 (Anti-Arrhythmia Agents); 0 (Pyrrolidines); 0 (Sodium Channel Blockers); 7B0ZZH8P2W (Pinacidil); 9G468C8B13 (vernakalant); A6IEZ5M406 (Ranolazine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160611
[St] Status:MEDLINE
[do] DOI:10.1111/jce.13029


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[PMID]:26997370
[Au] Autor:Yang YH; Zhang Y; Chen W; Wang Y; Cao S; Yu T; Wang H
[Ad] Endereço:Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China. Electronic address: yihuiyangzy@163.com.
[Ti] Título:Pinacidil-postconditioning is equivalent to ischemic postconditioning in defeating cardiac ischemia-reperfusion injury in rat.
[So] Source:Eur J Pharmacol;780:26-32, 2016 Jun 05.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Ischemic postconditioning (IPO) had been reported as a promising method against myocardial ischemia-reperfusion (I/R) injury, but IPO was later proved with poor clinical benefit. In this study, we compared the protective effects of pinacidil-postconditioning (PPO) and IPO against myocardial I/R injury. Langendorff rat hearts were randomly assigned to one of the following groups (n=8 each): Control group, I/R group (40min ischemia and 60min reperfusion), IPO group (6 successive cycles of 10s reperfusion per 10s occlusion before fully reperfusion), PPO group (perfused with 50µM pinacidil for 5min before reperfusion). Heart performance, infarct size and mitochondrial respiratory function were evaluated, and target genes/proteins of well-known Nuclear Factor-E2 Related Factor 2 (Nrf2) were assessed. Both IPO and PPO preserved heart function and myocardial ultrastructure at the end of reperfusion (all P<0.05 vs. I/R). The expression of Nrf2, NADH-quinone oxidoreductase-1 (NQO1), heme oxygenase 1 (HO-1) and superoxide dismutase 1 (SOD1) were similarly increased after IPO and PPO treatment (all P<0.05 vs. I/R). PPO exerted solid effect in defeating cardiac ischemia-reperfusion injury in rat.
[Mh] Termos MeSH primário: Vasos Coronários/efeitos dos fármacos
Pós-Condicionamento Isquêmico/métodos
Traumatismo por Reperfusão Miocárdica/fisiopatologia
Pinacidil/farmacologia
[Mh] Termos MeSH secundário: Animais
Respiração Celular/efeitos dos fármacos
Vasos Coronários/fisiopatologia
Hemodinâmica/efeitos dos fármacos
Masculino
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Traumatismo por Reperfusão Miocárdica/genética
Traumatismo por Reperfusão Miocárdica/metabolismo
Traumatismo por Reperfusão Miocárdica/patologia
Miocárdio/metabolismo
Miocárdio/patologia
Fator 2 Relacionado a NF-E2/metabolismo
Ratos
Ratos Sprague-Dawley
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-E2-Related Factor 2); 0 (Nfe2l2 protein, rat); 7B0ZZH8P2W (Pinacidil)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170306
[Lr] Data última revisão:
170306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160322
[St] Status:MEDLINE


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[PMID]:26976335
[Au] Autor:Philyppov IB; Golub AА; Boldyriev OI; Shtefan NL; Totska K; Voitychuk OI; Shuba YM
[Ad] Endereço:Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
[Ti] Título:Myorelaxant action of fluorine-containing pinacidil analog, flocalin, in bladder smooth muscle is mediated by inhibition of L-type calcium channels rather than activation of KATP channels.
[So] Source:Naunyn Schmiedebergs Arch Pharmacol;389(6):585-92, 2016 Jun.
[Is] ISSN:1432-1912
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Flocalin (FLO) is a new ATP-sensitive K(+) (KATP) channel opener (KCO) derived from pinacidil (PIN) by adding fluorine group to the drug's structure. FLO acts as a potent cardioprotector against ischemia-reperfusion damage in isolated heart and whole animal models primarily via activating cardiac-specific Kir6.2/SUR2A KATP channels. Given that FLO also confers relaxation on several types of smooth muscles and can partially inhibit L-type Ca(2+) channels, in this study, we asked what is the mechanism of FLO action in bladder detrusor smooth muscle (DSM). The actions of FLO and PIN on contractility of rat and guinea pig DSM strips and membrane currents of isolated DSM cells were compared by tensiometry and patch clamp. Kir6 and SUR subunit expression in rat DSM was assayed by reverse transcription PCR (RT-PCR). In contrast to PIN (10 µM), FLO (10 µM) did not produce glibenclamide-sensitive DSM strips' relaxation and inhibition of spontaneous and electrically evoked contractions. However, FLO, but not PIN, inhibited contractions evoked by high K(+) depolarization. FLO (40 µM) did not change the level of isolated DSM cell's background K(+) current, but suppressed by 20 % L-type Ca(2+) current. Determining various Kir6 and SUR messenger RNA (mRNA) expressions in rat DSM by RT-PCR indicated that dominant KATP channel in rat DSM is of vascular type involving association of Kir6.1 and SUR2B subunits. Myorelaxant effects of FLO in bladder DSM are explained by partial blockade of L-type Ca(2+) channel-mediated Ca(2+) influx rather than by hyperpolarization associated with increased K(+) permeability. Thus, insertion of fluorine group in PIN's structure made the drug more discriminative between Kir6.2/SUR2A cardiac- and Kir6.1/SUR2B vascular-type KATP channels and rendered it partial L-type Ca(2+) channel-blocking potency.
[Mh] Termos MeSH primário: Bloqueadores dos Canais de Cálcio/farmacologia
Canais de Cálcio Tipo L/efeitos dos fármacos
Canais KATP/agonistas
Relaxamento Muscular/efeitos dos fármacos
Músculo Liso/efeitos dos fármacos
Pinacidil/análogos & derivados
Bexiga Urinária/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Bloqueadores dos Canais de Cálcio/química
Canais de Cálcio Tipo L/metabolismo
Estimulação Elétrica
Cobaias
Técnicas In Vitro
Canais KATP/genética
Canais KATP/metabolismo
Masculino
Potenciais da Membrana
Estrutura Molecular
Músculo Liso/metabolismo
Pinacidil/química
Pinacidil/farmacologia
Ratos Wistar
Transdução de Sinais/efeitos dos fármacos
Relação Estrutura-Atividade
Receptores Sulfonilureia/agonistas
Receptores Sulfonilureia/metabolismo
Bexiga Urinária/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Blockers); 0 (Calcium Channels, L-Type); 0 (KATP Channels); 0 (N-(4-difluoromethoxyphenyl)-N'-pinacolyl-N''-cyanoguanidine); 0 (Sulfonylurea Receptors); 0 (uK-ATP-1 potassium channel); 7B0ZZH8P2W (Pinacidil)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160316
[St] Status:MEDLINE
[do] DOI:10.1007/s00210-016-1228-4


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[PMID]:26949448
[Au] Autor:Fan Z; Wen T; Chen Y; Huang L; Lin W; Yin C; Tan W
[Ad] Endereço:School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South Ch
[Ti] Título:Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes.
[So] Source:Oxid Med Cell Longev;2016:6362812, 2016.
[Is] ISSN:1942-0994
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:KATP channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of KATP channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcKATP channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcKATP channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria.
[Mh] Termos MeSH primário: Diazóxido/farmacologia
Diterpenos Caurânicos/farmacologia
Ventrículos do Coração/citologia
Mitocôndrias/metabolismo
Miócitos Cardíacos/metabolismo
Pinacidil/farmacologia
Sarcolema/metabolismo
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Potenciais de Ação/efeitos dos fármacos
Animais
Canais de Cálcio Tipo L/metabolismo
Flavoproteínas/metabolismo
Fluorescência
Glibureto/farmacologia
Cobaias
Ativação do Canal Iônico/efeitos dos fármacos
Canais KATP/metabolismo
Mitocôndrias/efeitos dos fármacos
Miócitos Cardíacos/efeitos dos fármacos
Oxirredução/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Sarcolema/efeitos dos fármacos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Calcium Channels, L-Type); 0 (Diterpenes, Kaurane); 0 (Flavoproteins); 0 (KATP Channels); 0 (Reactive Oxygen Species); 091QB7QO95 (isosteviol); 7B0ZZH8P2W (Pinacidil); O5CB12L4FN (Diazoxide); SX6K58TVWC (Glyburide); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160308
[St] Status:MEDLINE
[do] DOI:10.1155/2016/6362812


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[PMID]:26682579
[Au] Autor:Fernandes G; Dasai N; Kozlova N; Mojadadi A; Gall M; Drew E; Barratt E; Madamidola OA; Brown SG; Milne AM; Martins da Silva SJ; Whalley KM; Barratt CL; Jovanovic A
[Ad] Endereço:Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
[Ti] Título:A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels.
[So] Source:Hum Reprod;31(2):287-97, 2016 Feb.
[Is] ISSN:1460-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:STUDY QUESTION: Could drugs targeting ATP-sensitive K(+) (K(ATP)) channels prevent any spontaneous increase in intracellular Ca(2+) that may occur in human metaphase II (MII) oocytes under in vitro conditions? SUMMARY ANSWER: Pinacidil, a K(ATP) channel opener, and glibenclamide, a K(ATP) channel blocker, prevent a spontaneous increase in intracellular Ca(2+) in human MII oocytes. WHAT IS KNOWN ALREADY: The quality of the oocyte and maintenance of this quality during in vitro processing in the assisted reproductive technology (ART) laboratory is of critical importance to successful embryo development and a healthy live birth. Maintenance of Ca(2+) homeostasis is crucial for cell wellbeing and increased intracellular Ca(2+) levels is a well-established indicator of cell stress. STUDY DESIGN, SIZE, DURATION: Supernumerary human oocytes (n = 102) collected during IVF/ICSI treatment that failed to fertilize were used from October 2013 to July 2015. All experiments were performed on mature (MII) oocytes. Dynamics of intracellular Ca(2+) levels were monitored in oocytes in the following experimental groups: (i) Control, (ii) Dimethyl sulfoxide (DMSO; used to dissolve pinacidil, glibenclamide and 2,4-Dinitrophenol (DNP)), (iii) Pinacidil, (iv) Glibenclamide, (v) DNP: an inhibitor of oxidative phosphorylation, (vi) Pinacidil and DNP and (vii) Glibenclamide and DNP. PARTICIPANTS/MATERIALS/SETTINGS/METHODS: Oocytes were collected under sedation as part of routine treatment at an assisted conception unit from healthy women (mean ± SD) age 34.1 ± 0.6 years, n = 41. Those surplus to clinical use were donated for research. Oocytes were loaded with Fluo-3 Ca(2+)-sensitive dye, and monitored by laser confocal microscopy for 2 h at 10 min intervals. Time between oocyte collection and start of Ca(2+) monitoring was 80.4 ± 2.1 h. MAIN RESULTS AND THE ROLE OF CHANCE: Intracellular levels of Ca(2+) increased under in vitro conditions with no deliberate challenge, as shown by Fluo-3 fluorescence increasing from 61.0 ± 11.8 AU (AU = arbitrary units; n = 23) to 91.8 ± 14.0 AU (n = 19; P < 0.001) after 2 h of monitoring. Pinacidil (100 µM) inhibited this increase in Ca(2+) (85.3 ± 12.3 AU at the beginning of the experiment, 81.7 ± 11.0 AU at the end of the experiment; n = 13; P = 0.616). Glibenclamide (100 µM) also inhibited the increase in Ca(2+) (74.7 ± 10.6 AU at the beginning and 71.8 ± 10.9 AU at the end of the experiment; n = 13; P = 0.851. DNP (100 mM) induced an increase in intracellular Ca(2+) that was inhibited by glibenclamide (100 µM; n = 9) but not by pinacidil (100 µM; n = 5). LIMITATIONS, REASONS FOR CAUTION: Owing to clinical and ethical considerations, it was not possible to monitor Ca(2+) in MII oocytes immediately after retrieval. MII oocytes were available for our experimentation only after unsuccessful IVF or ICSI, which was, on average, 80.4 ± 2.1 h (n = 102 oocytes) after the moment of retrieval. As the MII oocytes used here were those that were not successfully fertilized, it is possible that they may have been abnormal with impaired Ca(2+) homeostasis and, furthermore, the altered Ca(2+) homeostasis might have been associated solely with the protracted incubation. WIDER IMPLICATIONS OF THE FINDINGS: These results show that maintenance of oocytes under in vitro conditions is associated with intracellular increase in Ca(2+), which can be counteracted by drugs targeting K(ATP) channels. As Ca(2+) homeostasis is crucial for contributing to a successful outcome of ART, these results suggest that K(ATP) channel openers and blockers should be tested as drugs for improving success rates of ART. STUDY FUNDING/COMPETING INTERESTS: University of Dundee, MRC (MR/K013343/1, MR/012492/1), NHS Tayside. Funding NHS fellowship (Dr Sarah Martins da Silva), NHS Scotland. The authors declare no conflicts of interest.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Técnicas de Maturação in Vitro de Oócitos/métodos
Moduladores de Transporte de Membrana/farmacologia
Oócitos/efeitos dos fármacos
Pinacidil/farmacologia
[Mh] Termos MeSH secundário: Técnicas de Cultura Embrionária
Homeostase
Modelos Biológicos
Oócitos/crescimento & desenvolvimento
Oócitos/metabolismo
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Membrane Transport Modulators); 7B0ZZH8P2W (Pinacidil); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151220
[St] Status:MEDLINE
[do] DOI:10.1093/humrep/dev300


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[PMID]:26548865
[Au] Autor:Slocinska M; Rosinski G; Jarmuszkiewicz W
[Ad] Endereço:Department of Animal Physiology and Development, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland. slocina@amu.edu.pl.
[Ti] Título:Activation of Mitochondrial Uncoupling Protein 4 and ATP-Sensitive Potassium Channel Cumulatively Decreases Superoxide Production in Insect Mitochondria.
[So] Source:Protein Pept Lett;23(1):63-8, 2016.
[Is] ISSN:1875-5305
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:It has been evidenced that mitochondrial uncoupling protein 4 (UCP4) and ATP-regulated potassium channel (mKATP channel) of insect Gromphadorhina coqereliana mitochondria decrease superoxide anion production. We elucidated whether the two energy-dissipating systems work together on a modulation of superoxide level in cockroach mitochondria. Our data show that the simultaneous activation of UCP4 by palmitic acid and mKATP channel by pinacidil revealed a cumulative effect on weakening mitochondrial superoxide formation. The inhibition of UCP4 by GTP (and/or ATP) and mKATP channel by ATP elevated superoxide production. These results suggest a functional cooperation of both energy-dissipating systems in protection against oxidative stress in insects.
[Mh] Termos MeSH primário: Baratas/metabolismo
Proteínas de Insetos/metabolismo
Canais KATP/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Superóxidos/metabolismo
[Mh] Termos MeSH secundário: Animais
Corpo Adiposo/metabolismo
Masculino
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Músculo Esquelético/metabolismo
Ácido Palmítico/farmacologia
Pinacidil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insect Proteins); 0 (KATP Channels); 0 (Membrane Transport Proteins); 11062-77-4 (Superoxides); 2V16EO95H1 (Palmitic Acid); 7B0ZZH8P2W (Pinacidil)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151110
[St] Status:MEDLINE



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