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[PMID]:28441750
[Au] Autor:Stockwell J; Jakova E; Cayabyab FS
[Ad] Endereço:Department of Surgery, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. jocelyn.stockwell@usask.ca.
[Ti] Título:Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration.
[So] Source:Molecules;22(4), 2017 Apr 23.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The inhibitory adenosine A1 receptor (A1R) and excitatory A2A receptor (A2AR) are predominantly expressed in the brain. Whereas the A2AR has been implicated in normal aging and enhancing neurotoxicity in multiple neurodegenerative diseases, the inhibitory A1R has traditionally been ascribed to have a neuroprotective function in various brain insults. This review provides a summary of the emerging role of prolonged A1R signaling and its potential cross-talk with A2AR in the cellular basis for increased neurotoxicity in neurodegenerative disorders. This A1R signaling enhances A2AR-mediated neurodegeneration, and provides a platform for future development of neuroprotective agents in stroke, Parkinson's disease and epilepsy.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Doenças Neurodegenerativas/metabolismo
Receptor A1 de Adenosina/fisiologia
Receptor A2A de Adenosina/fisiologia
[Mh] Termos MeSH secundário: Animais
Encéfalo/patologia
Seres Humanos
Doenças Neurodegenerativas/tratamento farmacológico
Fármacos Neuroprotetores/farmacologia
Agonistas Purinérgicos/farmacologia
Antagonistas Purinérgicos/farmacologia
Receptor Cross-Talk
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Neuroprotective Agents); 0 (Purinergic Agonists); 0 (Purinergic Antagonists); 0 (Receptor, Adenosine A1); 0 (Receptor, Adenosine A2A)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


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[PMID]:28039004
[Au] Autor:Munoz A; Yazdi IK; Tang X; Rivera C; Taghipour N; Grossman RG; Boone TB; Tasciotti E
[Ad] Endereço:Regenerative Medicine Program - Urology, Houston Methodist Research Institute, Houston, TX 77030, United States; Department of Urology, Houston Methodist Hospital, Houston, TX 77030, United States. Electronic address: AMunoz@HoustonMethodist.org.
[Ti] Título:Localized inhibition of P2X7R at the spinal cord injury site improves neurogenic bladder dysfunction by decreasing urothelial P2X3R expression in rats.
[So] Source:Life Sci;171:60-67, 2017 Feb 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Reestablishment of bladder function in patients with spinal cord injury (SCI) is a clinical priority. Our objectives were to determine whether SCI-localized inhibition of purinergic P2X7 receptors (P2X7R) improve bladder function by decreasing afferent signals mediated by urothelial P2X3R. MAIN METHODS: Systemic inhibition of P2X7R may improve locomotion in rodent SCI models; however, beneficial effects on bladder function and its physiological mechanisms have not been evaluated. We designed a thermosensitive nanohydrogel (NHG) consisting of the P2X7R antagonist brilliant blue-G (BBG) loaded into silica nanoparticles, embedded with poly(d,l-lactic-co-glycolic) acid, and resuspended in 20% pluronic acid. Female Sprague-Dawley rats with a bilateral dorsal lesion at the thoracic T8/T9 region received either 100µl of an empty NHG, or a NHG containing BBG (BBG-NHG) on top of the spinal tissue. Cystometric properties, spinal immunohistochemistry for P2X7R, and bladder immunohistochemistry for P2X3R were evaluated at four weeks post-SCI. KEY FINDINGS: After SCI animals recovered hind-legs use but neurogenic bladder dysfunction remained. SCI rats treated with BBG-NHG for a period of at least two weeks post-SCI experienced fewer non-voiding contractions. The localized inhibition of P2X7R decreased microglia activation. At the lower urinary tract level we observed, unexpectedly, a concomitant reduction of urothelial P2X3 receptors, which are involved in initiation of bladder afferent transmission to start micturition. SIGNIFICANCE: Localized inhibition of P2X7R for two weeks can be associated with reduced number of microglia and attenuated bladder hyperexcitability mediated by downregulation of urothelial P2X3R in rats with neurogenic bladder dysfunction and independently of locomotor improvements.
[Mh] Termos MeSH primário: Antagonistas Purinérgicos/farmacologia
Receptores Purinérgicos P2X3/metabolismo
Receptores Purinérgicos P2X7/efeitos dos fármacos
Traumatismos da Medula Espinal/metabolismo
Bexiga Urinaria Neurogênica/tratamento farmacológico
[Mh] Termos MeSH secundário: Actinas/metabolismo
Animais
Feminino
Hidrogéis
Antagonistas Purinérgicos/uso terapêutico
Ratos
Ratos Sprague-Dawley
Bexiga Urinária/efeitos dos fármacos
Bexiga Urinária/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Hydrogels); 0 (Purinergic Antagonists); 0 (Receptors, Purinergic P2X3); 0 (Receptors, Purinergic P2X7)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170406
[Lr] Data última revisão:
170406
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170101
[St] Status:MEDLINE


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[PMID]:27867013
[Au] Autor:Abdelrahman A; Namasivayam V; Hinz S; Schiedel AC; Köse M; Burton M; El-Tayeb A; Gillard M; Bajorath J; de Ryck M; Müller CE
[Ad] Endereço:PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
[Ti] Título:Characterization of P2X4 receptor agonists and antagonists by calcium influx and radioligand binding studies.
[So] Source:Biochem Pharmacol;125:41-54, 2017 Feb 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Antagonists for ATP-activated P2X4 ion channel receptors are currently in the focus as novel drug targets, in particular for the treatment of neuropathic and inflammatory pain. We stably expressed the human, rat and mouse P2X4 receptors in 1321N1 astrocytoma cells, which is devoid of functional nucleotide receptors, by retroviral transfection, and established monoclonal cell lines. Calcium flux assay conditions were optimized for high-throughput screening resulting in a Z'-factor of >0.8. The application of ready-to-use frozen cells did not negatively affect the results of the calcium assays, which is of great advantage for the screening of compound libraries. Species differences were observed, the rat P2X4 receptor being particularly insensitive to many ATP derivatives. Membrane preparations of the cell lines showed high levels of specific [ S]ATPγS binding with low nonspecific binding (<5% of total binding), while non-transfected cells were devoid of specific binding sites for the radioligand. Conditions were employed which allow binding studies to be performed at room temperature. While a variety of nucleotide-derived agonists and the antagonist TNP-ATP displaced [ S]ATPγS from its binding site at human P2X4 receptors, the non-nucleotidic antagonists paroxetine and 5-BDBD did not compete with radioligand binding and were therefore characterized as allosteric antagonists. Homology modeling was applied to find an explanation for the observed species differences.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Agonistas Purinérgicos/farmacologia
Antagonistas Purinérgicos/farmacologia
Receptores Purinérgicos P2X4/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Seres Humanos
Transporte de Íons
Camundongos
Ensaio Radioligante
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purinergic Agonists); 0 (Purinergic Antagonists); 0 (Receptors, Purinergic P2X4); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161122
[St] Status:MEDLINE


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[PMID]:27677282
[Au] Autor:Bol M; Wang N; De Bock M; Wacquier B; Decrock E; Gadicherla A; Decaluwé K; Vanheel B; van Rijen HV; Krysko DV; Bultynck G; Dupont G; Van de Voorde J; Leybaert L
[Ad] Endereço:Department of Basic Medical Sciences, Physiology Group, Faculty of Medicine & Health Sciences, Ghent University, De Pintelaan 185 (Block B, Room 031), 9000 Ghent, Belgium.
[Ti] Título:At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries.
[So] Source:Cardiovasc Res;113(2):195-206, 2017 Feb.
[Is] ISSN:1755-3245
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIMS: Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP. Here we investigated cross-talk between hemichannels and Ca /purinergic signalling in controlling blood vessel contraction. We hypothesized that hemichannel Ca entry and ATP release contributes to smooth muscle cell (SMC) Ca dynamics, thereby influencing vessel contractility. We applied several peptide modulators of hemichannel function and inhibitors of Ca and ATP signalling to investigate their influence on SMC Ca dynamics and vessel contractility. METHODS AND RESULTS: Confocal Ca imaging studies on small mesenteric arteries (SMAs) from rat demonstrated that norepinephrine-induced SMC Ca oscillations were inhibited by blocking IP receptors with xestospongin-C and by interfering with hemichannel function, most notably by the specific Cx43 hemichannel blocking peptide TAT-L2 and by TAT-CT9 that promotes Cx43 hemichannel opening. Evidence for hemichannel involvement in SMC function was supported by the fact that TAT-CT9 significantly increased SMC resting cytoplasmic Ca concentration, indicating it facilitated Ca entry, and by the observation that norepinephrine-triggered vessel ATP release was blocked by TAT-L2. Myograph tension measurements on isolated SMAs showed significant inhibition of norepinephrine-triggered contractility by the ATP receptor antagonist suramin, but the strongest effect was observed with TAT-L2 that gave ∼80% inhibition at 37 °C. TAT-L2 inhibition of vessel contraction was significantly reduced in conditional Cx43 knockout animals, indicating the effect was Cx43 hemichannel-dependent. Computational modelling suggested these results could be explained by the opening of a single hemichannel per SMC. CONCLUSIONS: These results indicate that Cx43 hemichannels contribute to SMC Ca dynamics and contractility, by facilitating Ca entry, ATP release, and purinergic signalling.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/metabolismo
Sinalização do Cálcio/efeitos dos fármacos
Cálcio/metabolismo
Comunicação Celular/efeitos dos fármacos
Conexina 43/antagonistas & inibidores
Junções Comunicantes/efeitos dos fármacos
Músculo Liso Vascular/efeitos dos fármacos
Miócitos de Músculo Liso/efeitos dos fármacos
Peptídeos/farmacologia
Vasoconstrição/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Animais
Simulação por Computador
Conexina 43/deficiência
Conexina 43/genética
Conexina 43/metabolismo
Conexinas/antagonistas & inibidores
Conexinas/metabolismo
Feminino
Junções Comunicantes/metabolismo
Genótipo
Técnicas In Vitro
Receptores de Inositol 1,4,5-Trifosfato/agonistas
Receptores de Inositol 1,4,5-Trifosfato/metabolismo
Artérias Mesentéricas/efeitos dos fármacos
Artérias Mesentéricas/metabolismo
Camundongos Knockout
Microscopia Confocal
Modelos Cardiovasculares
Músculo Liso Vascular/metabolismo
Miócitos de Músculo Liso/metabolismo
Norepinefrina/farmacologia
Fenótipo
Antagonistas Purinérgicos/farmacologia
Ratos Wistar
Fatores de Tempo
Vasoconstritores/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Connexin 43); 0 (Connexins); 0 (GJA1 protein, mouse); 0 (Inositol 1,4,5-Trisphosphate Receptors); 0 (Peptides); 0 (Purinergic Antagonists); 0 (Vasoconstrictor Agents); 0 (Vasodilator Agents); 0 (connexin 37); 0 (connexin 43 protein, rat); 8L70Q75FXE (Adenosine Triphosphate); SY7Q814VUP (Calcium); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160929
[St] Status:MEDLINE
[do] DOI:10.1093/cvr/cvw215


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[PMID]:27628008
[Au] Autor:Würtz M; Grove EL
[Ad] Endereço:Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. morten.wurtz@clin.au.dk.
[Ti] Título:Proton Pump Inhibitors in Cardiovascular Disease: Drug Interactions with Antiplatelet Drugs.
[So] Source:Adv Exp Med Biol;906:325-350, 2017.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aspirin and P2Y receptor antagonists are widely used across the spectrum of cardiovascular diseases. Upper gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed.PPIs provide gastroprotection by changing the intragastric milieu, essentially by raising intragastric pH. In recent years, it has been heavily discussed whether PPIs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Pharmacodynamic and pharmacokinetic studies suggested an interaction between PPIs and clopidogrel, and subsequent clinical studies were conducted to evaluate the clinical impact of this interaction. More recently, it was reported that PPIs may also attenuate the antiplatelet effect of aspirin. This may be clinically important, because a fixed combination of aspirin and a PPI (esomeprazole) has recently been approved and because aspirin is the most widely used drug in patients with cardiovascular disease. The antiplatelet effect of the new P2Y receptor antagonists, ticagrelor and prasugrel, seems less influenced by PPI co-treatment.Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition potentially carries considerable clinical impact. The present book chapter summarizes the evidence regarding the widespread use of platelet inhibitors and PPIs in combination. Moreover, it outlines current evidence supporting or opposing drug interactions between these drugs and discusses clinical implications.
[Mh] Termos MeSH primário: Aspirina/farmacocinética
Doenças Cardiovasculares/tratamento farmacológico
Esomeprazol/farmacocinética
Inibidores da Bomba de Prótons/farmacocinética
Antagonistas Purinérgicos/farmacocinética
Ticlopidina/análogos & derivados
[Mh] Termos MeSH secundário: Adenosina/análogos & derivados
Adenosina/uso terapêutico
Aspirina/sangue
Doenças Cardiovasculares/genética
Doenças Cardiovasculares/metabolismo
Doenças Cardiovasculares/patologia
Esquema de Medicação
Cálculos da Dosagem de Medicamento
Interações Medicamentosas
Esomeprazol/sangue
Hemorragia Gastrointestinal/induzido quimicamente
Hemorragia Gastrointestinal/metabolismo
Hemorragia Gastrointestinal/patologia
Expressão Gênica
Seres Humanos
Concentração de Íons de Hidrogênio/efeitos dos fármacos
Úlcera Péptica/induzido quimicamente
Úlcera Péptica/metabolismo
Úlcera Péptica/patologia
Cloridrato de Prasugrel/uso terapêutico
Inibidores da Bomba de Prótons/sangue
Antagonistas Purinérgicos/sangue
Receptores Purinérgicos P2Y12/genética
Receptores Purinérgicos P2Y12/metabolismo
Ticlopidina/sangue
Ticlopidina/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (P2RY12 protein, human); 0 (Proton Pump Inhibitors); 0 (Purinergic Antagonists); 0 (Receptors, Purinergic P2Y12); A74586SNO7 (clopidogrel); G89JQ59I13 (Prasugrel Hydrochloride); GLH0314RVC (Ticagrelor); K72T3FS567 (Adenosine); N3PA6559FT (Esomeprazole); OM90ZUW7M1 (Ticlopidine); R16CO5Y76E (Aspirin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160916
[St] Status:MEDLINE


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[PMID]:27589594
[Au] Autor:Min YW; Hong YS; Ko EJ; Lee JY; Ahn KD; Bae JM; Rhee PL
[Ad] Endereço:Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
[Ti] Título:Nitrergic Pathway Is the Main Contributing Mechanism in the Human Gastric Fundus Relaxation: An In Vitro Study.
[So] Source:PLoS One;11(9):e0162146, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles. METHODS: Gastric fundus muscle strips (12 circular and 13 longitudinal) were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s). To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 µM), MRS2500 (a purinergic P2Y1 receptor antagonist, 1 µM), and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 µM) were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement. RESULTS: In spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz) uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle). Tetrodotoxin abolished any EFS-induced motor response. CONCLUSIONS: The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation.
[Mh] Termos MeSH primário: Fundo Gástrico/efeitos dos fármacos
Motilidade Gastrointestinal/efeitos dos fármacos
Contração Muscular/efeitos dos fármacos
Relaxamento Muscular/efeitos dos fármacos
Músculo Liso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Atropina/farmacologia
Nucleotídeos de Desoxiadenina/farmacologia
Estimulação Elétrica
Inibidores Enzimáticos/farmacologia
Feminino
Fundo Gástrico/fisiologia
Motilidade Gastrointestinal/fisiologia
Seres Humanos
Masculino
Meia-Idade
Antagonistas Muscarínicos/farmacologia
Contração Muscular/fisiologia
Relaxamento Muscular/fisiologia
Músculo Liso/fisiologia
Óxido Nítrico Sintase/antagonistas & inibidores
Nitroarginina/farmacologia
Antagonistas Purinérgicos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate); 0 (Deoxyadenine Nucleotides); 0 (Enzyme Inhibitors); 0 (Muscarinic Antagonists); 0 (Purinergic Antagonists); 2149-70-4 (Nitroarginine); 7C0697DR9I (Atropine); EC 1.14.13.39 (Nitric Oxide Synthase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0162146


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[PMID]:27006168
[Au] Autor:Gonzalez EJ; Heppner TJ; Nelson MT; Vizzard MA
[Ad] Endereço:Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, 05405, USA.
[Ti] Título:Purinergic signalling underlies transforming growth factor-ß-mediated bladder afferent nerve hyperexcitability.
[So] Source:J Physiol;594(13):3575-88, 2016 Jul 01.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:KEY POINTS: The sensory components of the urinary bladder are responsible for the transduction of bladder filling and are often impaired with neurological injury or disease. Elevated extracellular ATP contributes, in part, to bladder afferent nerve hyperexcitability during urinary bladder inflammation or irritation. Transforming growth factor-ß1 (TGF-ß1) may stimulate ATP release from the urothelium through vesicular exocytosis mechanisms with minimal contribution from pannexin-1 channels to increase bladder afferent nerve discharge. Bladder afferent nerve hyperexcitability and urothelial ATP release with CYP-induced cystitis is decreased with TGF-ß inhibition. These results establish a causal link between an inflammatory mediator, TGF-ß, and intrinsic signalling mechanisms of the urothelium that may contribute to the altered sensory processing of bladder filling. ABSTRACT: The afferent limb of the micturition reflex is often compromised following bladder injury, disease and inflammatory conditions. We have previously demonstrated that transforming growth factor-ß (TGF-ß) signalling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Despite the functional presence of TGF-ß in bladder inflammation, the precise mechanisms of TGF-ß mediating bladder dysfunction are not yet known. Thus, the present studies investigated the sensory components of the urinary bladder that may underlie the pathophysiology of aberrant TGF-ß activation. We utilized bladder-pelvic nerve preparations to characterize bladder afferent nerve discharge and the mechanisms of urothelial ATP release with distention. Our findings indicate that bladder afferent nerve discharge is sensitive to elevated extracellular ATP during pathological conditions of urinary bladder inflammation or irritation. We determined that TGF-ß1 may increase bladder afferent nerve excitability by stimulating ATP release from the urothelium via vesicular exocytosis mechanisms with minimal contribution from pannexin-1 channels. Furthermore, blocking aberrant TGF-ß signalling in cyclophosphamide-induced cystitis with TßR-1 inhibition decreased afferent nerve hyperexcitability with a concomitant decrease in urothelial ATP release. Taken together, these results establish a role for purinergic signalling mechanisms in TGF-ß-mediated bladder afferent nerve activation that may ultimately facilitate increased voiding frequency. The synergy between intrinsic urinary bladder signalling mechanisms and an inflammatory mediator provides novel insight into bladder dysfunction and supports new avenues for therapeutic intervention.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/fisiologia
Cistite/fisiopatologia
Receptores Purinérgicos/fisiologia
Fator de Crescimento Transformador beta/fisiologia
Bexiga Urinária/inervação
Bexiga Urinária/fisiologia
[Mh] Termos MeSH secundário: Animais
Conexinas/fisiologia
Ciclofosfamida
Cistite/induzido quimicamente
Masculino
Camundongos Endogâmicos C57BL
Proteínas do Tecido Nervoso/fisiologia
Proteínas Serina-Treonina Quinases/fisiologia
Antagonistas Purinérgicos/farmacologia
Fosfato de Piridoxal/análogos & derivados
Fosfato de Piridoxal/farmacologia
Receptores de Fatores de Crescimento Transformadores beta/fisiologia
Transdução de Sinais
Urotélio/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Connexins); 0 (Nerve Tissue Proteins); 0 (Panx1 protein, mouse); 0 (Purinergic Antagonists); 0 (Receptors, Purinergic); 0 (Receptors, Transforming Growth Factor beta); 0 (Transforming Growth Factor beta); 149017-66-3 (pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid); 5V5IOJ8338 (Pyridoxal Phosphate); 8L70Q75FXE (Adenosine Triphosphate); 8N3DW7272P (Cyclophosphamide); EC 2.7.1.11 (TGF-beta type I receptor); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160324
[St] Status:MEDLINE
[do] DOI:10.1113/JP272148


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[PMID]:26920010
[Au] Autor:Burnstock G
[Ad] Endereço:Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, United Kingdom; Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Australia. Electronic address: g.burnstock@ucl.ac.uk.
[Ti] Título:Purinergic Mechanisms and Pain.
[So] Source:Adv Pharmacol;75:91-137, 2016.
[Is] ISSN:1557-8925
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is a brief introductory summary of purinergic signaling involving ATP storage, release, and ectoenzymatic breakdown, and the current classification of receptor subtypes for purines and pyrimidines. The review then describes purinergic mechanosensory transduction involved in visceral, cutaneous, and musculoskeletal nociception and on the roles played by receptor subtypes in neuropathic and inflammatory pain. Multiple purinoceptor subtypes are involved in pain pathways both as an initiator and modulator. Activation of homomeric P2X3 receptors contributes to acute nociception and activation of heteromeric P2X2/3 receptors appears to modulate longer-lasting nociceptive sensitivity associated with nerve injury or chronic inflammation. In neuropathic pain activation of P2X4, P2X7, and P2Y12 receptors on microglia may serve to maintain nociceptive sensitivity through complex neural-glial cell interactions and antagonists to these receptors reduce neuropathic pain. Potential therapeutic approaches involving purinergic mechanisms will be discussed.
[Mh] Termos MeSH primário: Dor/metabolismo
Receptores Purinérgicos/metabolismo
[Mh] Termos MeSH secundário: Analgésicos/farmacologia
Analgésicos/uso terapêutico
Animais
Seres Humanos
Mecanotransdução Celular
Transtornos de Enxaqueca/metabolismo
Dor/tratamento farmacológico
Antagonistas Purinérgicos/farmacologia
Antagonistas Purinérgicos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics); 0 (Purinergic Antagonists); 0 (Receptors, Purinergic)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160228
[St] Status:MEDLINE


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[PMID]:26527433
[Au] Autor:Krueger D; Michel K; Zeller F; Demir IE; Ceyhan GO; Slotta-Huspenina J; Schemann M
[Ad] Endereço:Human Biology, Technische Universität München, Freising, Germany.
[Ti] Título:Neural influences on human intestinal epithelium in vitro.
[So] Source:J Physiol;594(2):357-72, 2016 Jan 15.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:KEY POINTS: We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine. We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens. ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine. The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut. ABSTRACT: Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1 antagonist] VIPergic together with L-NAME-sensitive nitrergic components dominated the ISC-EFS in colonic preparations. Differences in numbers of cholinergic or VIPergic neurons, sensitivity of epithelial muscarinic or VIP receptors, or stimulus frequency-dependent transmitter release were not responsible for the region-specific transmitter contribution to ISC-EFS. Instead, the low atropine-sensitivity of ISC-EFS in the colon was the result of high cholinesterase activity because neostigmine revealed cholinergic components. Colonic ISC-EFS remained unchanged after tachykinin, P2X, P2Y or A1 and A2 receptor blockade. R-basal was smaller and ISC-basal was higher in the small intestine. TTX and bumetanide decreased ISC-basal in all regions, suggesting nerve-dependent secretory tone. ISC-basal was atropine-sensitive in the small intestine and PG97-269-sensitive in the large intestine. This comprehensive study reveals novel insights into region-specific nerve-mediated secretion in the human small and large intestine.
[Mh] Termos MeSH primário: Potenciais de Ação
Mucosa Intestinal/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Bicarbonatos/metabolismo
Cloretos/metabolismo
Seres Humanos
Mucosa Intestinal/efeitos dos fármacos
Mucosa Intestinal/inervação
Intestino Grosso/citologia
Intestino Grosso/inervação
Intestino Grosso/metabolismo
Intestino Delgado/citologia
Intestino Delgado/inervação
Intestino Delgado/metabolismo
Transporte de Íons
Meia-Idade
Antagonistas Muscarínicos/farmacologia
Neurônios/fisiologia
Óxido Nítrico/metabolismo
Bloqueadores dos Canais de Potássio/farmacologia
Antagonistas Purinérgicos/farmacologia
Bloqueadores dos Canais de Sódio/farmacologia
Peptídeo Intestinal Vasoativo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bicarbonates); 0 (Chlorides); 0 (Muscarinic Antagonists); 0 (Potassium Channel Blockers); 0 (Purinergic Antagonists); 0 (Sodium Channel Blockers); 31C4KY9ESH (Nitric Oxide); 37221-79-7 (Vasoactive Intestinal Peptide)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170118
[Lr] Data última revisão:
170118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151104
[St] Status:MEDLINE
[do] DOI:10.1113/JP271493


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[PMID]:25502294
[Au] Autor:Gubert C; Fries GR; Pfaffenseller B; Ferrari P; Coutinho-Silva R; Morrone FB; Kapczinski F; Battastini AMO
[Ad] Endereço:Programa de Pós-Graduação Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
[Ti] Título:Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine.
[So] Source:Mol Neurobiol;53(1):611-620, 2016 Jan.
[Is] ISSN:1559-1182
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The objective of this study was to explore the association between the P2X7 purinergic receptor (P2X7R) and neuroinflammation using a preclinical model of acute bipolar mania. We analyzed the modulatory effects of P2X7R agonist (3'-O-(4-benzoyl)benzoyl-adenosine 5'-triphosphate, BzATP) and antagonists (brilliant blue, BBG and 3-[[5-(2,3 dichlorophenyl)-1H-tetrazol-1-yl]methyl]pyridine hydrochloride, A438079) on assessments related to behavior (locomotor activity), neuroinflammation (interleukin-1 beta, IL-1ß; tumor necrosis factor alpha, TNF-α; and interleukin- 6, IL-6), oxidative stress (thiobarbituric acid reactive substances, TBARS) and neuroplasticity (brain-derived neurotrophic factor, BDNF) markers in a pharmacological model of mania induced by acute and chronic treatment with D-amphetamine (AMPH) (2 mg/kg) in mice. An apparent lack of responsiveness to AMPH was observed in terms of the locomotor activity in animals with blocked P2X7R or with genetic deletion of P2X7R in knockout (P2X7R(-/-)) mice. Likewise, P2X7R participated in the AMPH-induced increase of the proinflammatory and excitotoxic environment, as demonstrated by the reversal of IL-1ß, TNF-α, and TBARS levels caused by P2X7R blocking. Our results support the hypothesis that P2X7R plays a role in the neuroinflammation induced by AMPH in a preclinical model of mania, which could explain the altered behavior. The present data suggest that P2X7R may be a therapeutic target related to the neuroinflammation reported in bipolar disorder.
[Mh] Termos MeSH primário: Transtorno Bipolar/induzido quimicamente
Transtorno Bipolar/metabolismo
Dextroanfetamina/toxicidade
Modelos Animais de Doenças
Receptores Purinérgicos P2X7/fisiologia
[Mh] Termos MeSH secundário: Animais
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Mediadores da Inflamação/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos CBA
Camundongos Knockout
Agonistas Purinérgicos/farmacologia
Antagonistas Purinérgicos/farmacologia
Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Inflammation Mediators); 0 (Purinergic Agonists); 0 (Purinergic Antagonists); 0 (Receptors, Purinergic P2X7); 0 (Thiobarbituric Acid Reactive Substances); TZ47U051FI (Dextroamphetamine)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141216
[St] Status:MEDLINE
[do] DOI:10.1007/s12035-014-9031-z



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