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[PMID]:27514482
[Au] Autor:Palmer G; Hibberd TJ; Roose T; Brookes SJ; Taylor M
[Ad] Endereço:Bioengineering Research Group, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom.
[Ti] Título:Measurement of strains experienced by viscerofugal nerve cell bodies during mechanosensitive firing using digital image correlation.
[So] Source:Am J Physiol Gastrointest Liver Physiol;311(5):G869-G879, 2016 Nov 01.
[Is] ISSN:1522-1547
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mechanosensory neurons detect physical events in the local environments of the tissues that they innervate. Studies of mechanosensitivity of neurons or nerve endings in the gut have related their firing to strain, wall tension, or pressure. Digital image correlation (DIC) is a technique from materials engineering that can be adapted to measure the local physical environments of afferent neurons at high resolution. Flat-sheet preparations of guinea pig distal colon were set up with arrays of tissue markers in vitro. Firing of single viscerofugal neurons was identified in extracellular colonic nerve recordings. The locations of viscerofugal nerve cell bodies were inferred by mapping firing responses to focal application of the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide. Mechanosensory firing was recorded during load-evoked uniaxial or biaxial distensions. Distension caused movement of surface markers which was captured by video imaging. DIC tracked the markers, interpolating the mechanical state of the gut at the location of the viscerofugal nerve cell body. This technique revealed heterogeneous load-evoked strain within preparations. Local strains at viscerofugal nerve cell bodies were usually smaller than global strain measurements and correlated more closely with mechanosensitive firing. Both circumferential and longitudinal strain activated viscerofugal neurons. Simultaneous loading in circumferential and longitudinal axes caused the highest levels of viscerofugal neuron firing. Multiaxial strains, reflecting tissue shearing and changing area, linearly correlated with mechanosensory firing of viscerofugal neurons. Viscerofugal neurons were mechanically sensitive to both local circumferential and local longitudinal gut strain, and appear to lack directionality in their stretch sensitivity.
[Mh] Termos MeSH primário: Potenciais de Ação/fisiologia
Colo/fisiologia
Mecanorreceptores/fisiologia
Neurônios/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Colo/efeitos dos fármacos
Colo/inervação
Iodeto de Dimetilfenilpiperazina/farmacologia
Feminino
Cobaias
Masculino
Mecanorreceptores/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Agonistas Nicotínicos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nicotinic Agonists); 54-77-3 (Dimethylphenylpiperazinium Iodide)
[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:160813
[St] Status:MEDLINE
[do] DOI:10.1152/ajpgi.00397.2015


  2 / 712 MEDLINE  
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[PMID]:25108310
[Au] Autor:Hay YA; Andjelic S; Badr S; Lambolez B
[Ad] Endereço:UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France. audrey.hay@normalesup.org.
[Ti] Título:Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs.
[So] Source:Brain Struct Funct;220(6):3497-512, 2015 Nov.
[Is] ISSN:1863-2661
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Neocortical layer VI is critically involved in thalamocortical activity changes during the sleep/wake cycle. It receives dense projections from thalamic nuclei sensitive to the wake-promoting neuropeptides orexins, and its deepest part, layer VIb, is the only cortical lamina reactive to orexins. This convergence of wake-promoting inputs prompted us to investigate how layer VIb can modulate cortical arousal, using patch-clamp recordings and optogenetics in rat brain slices. We found that the majority of layer VIb neurons were excited by nicotinic agonists and orexin through the activation of nicotinic receptors containing α4-α5-ß2 subunits and OX2 receptor, respectively. Specific effects of orexin on layer VIb neurons were potentiated by low nicotine concentrations and we used this paradigm to explore their intracortical projections. Co-application of nicotine and orexin increased the frequency of excitatory post-synaptic currents in the ipsilateral cortex, with maximal effect in infragranular layers and minimal effect in layer IV, as well as in the contralateral cortex. The ability of layer VIb to relay thalamocortical inputs was tested using photostimulation of channelrhodopsin-expressing fibers from the orexin-sensitive rhomboid nucleus in the parietal cortex. Photostimulation induced robust excitatory currents in layer VIa neurons that were not pre-synaptically modulated by orexin, but exhibited a delayed, orexin-dependent, component. Activation of layer VIb by orexin enhanced the reliability and spike-timing precision of layer VIa responses to rhomboid inputs. These results indicate that layer VIb acts as an orexin-gated excitatory feedforward loop that potentiates thalamocortical arousal.
[Mh] Termos MeSH primário: Córtex Cerebral/fisiologia
Núcleos da Linha Média do Tálamo/fisiologia
Neurônios/fisiologia
Orexinas/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Córtex Cerebral/efeitos dos fármacos
Iodeto de Dimetilfenilpiperazina/farmacologia
Neurônios GABAérgicos/efeitos dos fármacos
Neurônios GABAérgicos/fisiologia
Masculino
Rede Nervosa/efeitos dos fármacos
Rede Nervosa/fisiologia
Vias Neurais/efeitos dos fármacos
Vias Neurais/fisiologia
Neurônios/efeitos dos fármacos
Agonistas Nicotínicos/farmacologia
Optogenética
Orexinas/administração & dosagem
Ratos
Ratos Wistar
Potenciais Sinápticos/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nicotinic Agonists); 0 (Orexins); 54-77-3 (Dimethylphenylpiperazinium Iodide)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150921
[Lr] Data última revisão:
150921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140811
[St] Status:MEDLINE
[do] DOI:10.1007/s00429-014-0869-7


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[PMID]:25660404
[Au] Autor:Watson BM; Oliveria JP; Nusca GM; Smith SG; Beaudin S; Dua B; Watson RM; Assayag EI; Cormier YF; Sehmi R; Gauvreau GM
[Ad] Endereço:Department of Medicine, McMaster University, Hamilton, Ont., Canada.
[Ti] Título:Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.
[So] Source:Int Arch Allergy Immunol;165(4):255-64, 2014.
[Is] ISSN:1423-0097
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. OBJECTIVE: We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. METHODS: Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. RESULTS: nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05). The effect of ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). CONCLUSION: This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses.
[Mh] Termos MeSH primário: Asma/imunologia
Basófilos/imunologia
Iodeto de Dimetilfenilpiperazina/análogos & derivados
Agonistas Nicotínicos/farmacologia
Receptores Nicotínicos/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Asma/tratamento farmacológico
Estudos Cross-Over
Iodeto de Dimetilfenilpiperazina/administração & dosagem
Iodeto de Dimetilfenilpiperazina/farmacologia
Método Duplo-Cego
Feminino
Citometria de Fluxo
Seres Humanos
Leucócitos Mononucleares
Masculino
Meia-Idade
Agonistas Nicotínicos/administração & dosagem
Diester Fosfórico Hidrolases/sangue
Pirofosfatases/sangue
Distribuição Aleatória
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ENPP3 protein, human); 0 (Nicotinic Agonists); 0 (Receptors, Nicotinic); 54-77-3 (Dimethylphenylpiperazinium Iodide); EC 3.1.4.- (Phosphoric Diester Hydrolases); EC 3.6.1.- (Pyrophosphatases)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:150209
[Lr] Data última revisão:
150209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150210
[St] Status:MEDLINE
[do] DOI:10.1159/000370068


  4 / 712 MEDLINE  
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[PMID]:25070830
[Au] Autor:Murad HA; Hasanin AH
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia. helmy_amany@yahoo.com.
[Ti] Título:The anti-inflammatory effects of 1,1 dimethyl-4-phenylpiperazinium (DMPP) compared to dexamethasone in a guinea pig model of ovalbumin induced asthma.
[So] Source:Eur Rev Med Pharmacol Sci;18(15):2228-36, 2014.
[Is] ISSN:2284-0729
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIM: Inflammatory cells involved in the pathophysiology of asthma express nicotinic receptor. Therefore 1,1 dimethyl(-4-)phenylpiperazinium (DMPP) in two doses were compared to dexamethasone in asthmatic guinea pigs. MATERIALS AND METHODS: Six groups were included; Normal control and five asthmatic (OVA-sensitized and challenged) groups; which were treated for 10 days as follows: two vehicles, dexamethasone (DEXA, 1 mg/kg) and DMPP (0.4 and 0.8 mg/kg) groups. Pulmonary functions and airway hyper-responsiveness were assessed. Leukocytic count, tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6) and immunoglobulin E (IgE) were measured in both blood and bronchoalveolar lavage fluid (BALF). Histopathological examination of the lung tissues was conducted. RESULTS: Asthmatic untreated animals exhibited significant increase in early and late airway resistance (RxV) and airway hyper-responsiveness, with reduction in tidal volume. Both blood and BALF showed significant increase in total leukocytic count (TLC), eosinophils, lymphocytes, monocytes, TNF-α, IL-6 and IgE with significant decrease in neutrophils. Airway inflammatory cell infiltration and smooth muscle thickness significantly increased. DMPP 0.4 mg/kg significantly decreased late phase RXV, TLC, BALF lymphocytes, TNF-α, smooth muscle thickness and increased neutrophils in BALF over both DEXA and DMPP 0.8 mg/kg. Moreover, DMPP 0.4 mg/kg significantly decreased IL-6 and BALF eosinophils than DMPP 0.8 mg/kg and decreased serum IgE and parenchymal inflammatory infiltration than DEXA. CONCLUSIONS: Low dose DMPP has more anti-inflammatory effect than a high dose in most parameters and sometimes than dexamethasone. Cholinergic anti-inflammatory pathway may therefore represent a potential drug target for allergic asthma. The dose related effect of DMPP and the mechanism underlying this effect require further evaluation.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Asma/induzido quimicamente
Asma/tratamento farmacológico
Dexametasona/farmacologia
Iodeto de Dimetilfenilpiperazina/farmacologia
Ovalbumina/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Antiasmáticos/farmacologia
Asma/metabolismo
Líquido da Lavagem Broncoalveolar/química
Modelos Animais de Doenças
Eosinófilos/efeitos dos fármacos
Eosinófilos/metabolismo
Cobaias
Imunoglobulina E/metabolismo
Interleucina-6/metabolismo
Contagem de Leucócitos/métodos
Pulmão/efeitos dos fármacos
Pulmão/metabolismo
Linfócitos/efeitos dos fármacos
Linfócitos/metabolismo
Masculino
Monócitos/efeitos dos fármacos
Monócitos/metabolismo
Músculo Liso/efeitos dos fármacos
Músculo Liso/metabolismo
Neutrófilos/efeitos dos fármacos
Neutrófilos/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Asthmatic Agents); 0 (Anti-Inflammatory Agents); 0 (Interleukin-6); 0 (Tumor Necrosis Factor-alpha); 37341-29-0 (Immunoglobulin E); 54-77-3 (Dimethylphenylpiperazinium Iodide); 7S5I7G3JQL (Dexamethasone); 9006-59-1 (Ovalbumin)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:140729
[Lr] Data última revisão:
140729
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140730
[St] Status:MEDLINE


  5 / 712 MEDLINE  
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[PMID]:24491353
[Au] Autor:Kayano T; Kitamura N; Miyazaki S; Ichiyanagi T; Shimomura N; Shibuya I; Aimi T
[Ad] Endereço:Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
[Ti] Título:Gymnopilins, a product of a hallucinogenic mushroom, inhibit the nicotinic acetylcholine receptor.
[So] Source:Toxicon;81:23-31, 2014 Apr.
[Is] ISSN:1879-3150
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gymnopilins are substances produced in fruiting bodies of the hallucinogenic mushroom, Gymnopilus junonius. Although, only a few biological effects of gymnopilins on animal tissues have been reported, it is believed that gymnopilins are a key factor of the G. junonius poisoning. In the present study, we found that gymnopilins inhibited ACh-evoked responses in neuronal cell line, PC12 cell, and determine the underlying mechanism. Gymnopilins were purified from wild fruiting bodies of G. junonius collected in Japan. Ca(2+)-imaging revealed that gymnopilins reduced the amplitude of ACh-evoked [Ca(2+)]i rises by about 50% and abolished the ACh responses remaining in the presence of atropine. Gymnopilins greatly reduced the amplitude of [Ca(2+)]i rises evoked by nicotinic ACh receptor agonists, 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP) and nicotine. In the whole-cell voltage clamp recording, gymnopilins inhibited the DMPP-evoked currents, but did not affect the voltage-gated Ca(2+) channel currents. These results indicate that gymnopilins directly act on nicotinic ACh receptors and inhibit their activity. This biological action of gymnopilins may be one of the causes of the G. junonius poisoning.
[Mh] Termos MeSH primário: Agaricales/química
Alucinógenos/farmacologia
Receptores Nicotínicos/metabolismo
Terpenos/farmacologia
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Animais
Cálcio
Iodeto de Dimetilfenilpiperazina/farmacologia
Alucinógenos/química
Nicotina/farmacologia
Células PC12
Técnicas de Patch-Clamp
Ratos
Terpenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hallucinogens); 0 (Receptors, Nicotinic); 0 (Terpenes); 54-77-3 (Dimethylphenylpiperazinium Iodide); 6M3C89ZY6R (Nicotine); N9YNS0M02X (Acetylcholine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140205
[St] Status:MEDLINE


  6 / 712 MEDLINE  
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[PMID]:24162003
[Au] Autor:He YQ; Li Y; Wang XY; He XD; Jun L; Chuai M; Lee KK; Wang J; Wang LJ; Yang X
[Ad] Endereço:Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology & Embryology, Medical College, Jinan University, Guangzhou 510632, China.
[Ti] Título:Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis.
[So] Source:Exp Cell Res;320(2):354-64, 2014 Jan 15.
[Is] ISSN:1090-2422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis - possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis.
[Mh] Termos MeSH primário: Iodeto de Dimetilfenilpiperazina/farmacologia
Glioma/irrigação sanguínea
Glioma/patologia
Neovascularização Patológica/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Embrião de Galinha
Seres Humanos
Indução de Remissão
Carga Tumoral/efeitos dos fármacos
Células Tumorais Cultivadas
Saco Vitelino/irrigação sanguínea
Saco Vitelino/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
54-77-3 (Dimethylphenylpiperazinium Iodide)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:131224
[Lr] Data última revisão:
131224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131029
[St] Status:MEDLINE


  7 / 712 MEDLINE  
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[PMID]:23867087
[Au] Autor:Leng J; Guan Q; Sun T; Wu Y; Cao Y; Guo Y
[Ad] Endereço:Shanghai Mass Spectrometry Center, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032 Shanghai, China.
[Ti] Título:Application of isotope-based carboxy group derivatization in LC-MS/MS analysis of tissue free-fatty acids for thyroid carcinoma.
[So] Source:J Pharm Biomed Anal;84:256-62, 2013 Oct.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Free fatty acids (FFAs) analysis of human tissue is challenging due to the low abundance of tissue lipids and interference from the complex matrix. Based on our previously reported on 2,4-dimethoxy-6-piperazin-1-yl pyrimidine (DMPP) derivatization toward carboxy group, we have further applied DMPP derivatization method in the assay of tissue FFAs in patients with thyroid carcinoma after method optimization including sample pretreatment, and derivatization condition. d6-DMPP labeled mixture of FFAs standard was used as the internal standard (IS). The d0-DMPP labeled samples (spiked with IS) were subsequently used for lipids profiling by selective reaction monitoring (SRM) detection. The DMPP derivatization combined with SRM not only allowed trace analysis of FFAs in complex matrix due to the extremely high sensitivity, but also minimized the errors in quantitation because of the very similar property between d0-DMPP derivatized samples and d6-DMPP derivatized IS. Eighteen kinds of FFAs were detected successfully with the increased level in carcinoma tissue compared with the normal tissue, which may be the results of abnormality in the metabolism of fatty acid synthases and lipids. Application of the DMPP based FFAs derivatization is expected to provide a promising tool for the investigation of lipids in vivo, especially for the research of lipid metabolism.
[Mh] Termos MeSH primário: Ácidos Carboxílicos/química
Cromatografia Líquida/métodos
Ácidos Graxos não Esterificados/análise
Espectrometria de Massas em Tandem/métodos
Neoplasias da Glândula Tireoide/química
[Mh] Termos MeSH secundário: Iodeto de Dimetilfenilpiperazina/química
Ácidos Graxos não Esterificados/química
Seres Humanos
Marcação por Isótopo/métodos
Isótopos/química
Metabolismo dos Lipídeos
Lipídeos/química
Sensibilidade e Especificidade
Neoplasias da Glândula Tireoide/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carboxylic Acids); 0 (Fatty Acids, Nonesterified); 0 (Isotopes); 0 (Lipids); 54-77-3 (Dimethylphenylpiperazinium Iodide)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:130729
[Lr] Data última revisão:
130729
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130723
[St] Status:MEDLINE


  8 / 712 MEDLINE  
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[PMID]:23461847
[Au] Autor:Ochi K; Teraoka H; Unno T; Komori S; Yamada M; Kitazawa T
[Ad] Endereço:Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
[Ti] Título:A ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium, caused both cholinergic and adrenergic responses in the isolated mouse atrium.
[So] Source:Eur J Pharmacol;704(1-3):7-14, 2013 Mar 15.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:An isolated atrial preparation of the mouse is useful for analyzing the actions of drugs on the myocardium, autonomic neurons and endocardial endothelium. The aim of the present study was to examine the functions of intrinsic neurons of the atrium using a ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium (DMPP). DMPP (1-100 µM) caused a negative chronotropic action followed by a positive chronotropic action in spontaneously beating right atria and also caused biphasic inotropic actions consisting of initial inhibition followed by potentiation of electrical field stimulation (EFS)-induced contraction in the left atria. Inotropic actions in the left atria induced by DMPP were characterized using some autonomic drugs and M2 and/or M3 muscarinic receptor knockout (M2R-KO, M3R-KO and M2M3R-KO) mice. Atropine and hexamethonium decreased the initial negative inotropic actions of DMPP. In the atria from pertussis toxin-treated, M2R-KO and M2/M3R-KO mice, the negative inotropic actions were abolished. On the other hand, the following positive inotropic actions were decreased by hexamethonium, atropine and atenolol. In the atria from reserpine-treated mice, positive inotropic actions were also decreased. The positive inotropic action induced by DMPP was almost the same in M2R-KO mice but was reduced in both M3R-KO mice and M2/M3R-KO mice. In conclusion, DMPP caused biphasic inotropic/chronotropic actions in the mouse atrium through activation of intrinsic cholinergic and adrenergic neurons. M2 and M3 muscarinic receptors and ß1-adrenoceptor are thought to be involved in these actions.
[Mh] Termos MeSH primário: Iodeto de Dimetilfenilpiperazina/farmacologia
Estimulantes Ganglionares/farmacologia
Átrios do Coração/efeitos dos fármacos
Receptor Muscarínico M2/fisiologia
Receptor Muscarínico M3/fisiologia
Receptores Adrenérgicos beta 1/fisiologia
[Mh] Termos MeSH secundário: Antagonistas de Receptores Adrenérgicos beta 1/farmacologia
Animais
Atenolol/farmacologia
Atropina/farmacologia
Inibidores da Colinesterase/farmacologia
Estimulação Elétrica
Feminino
Frequência Cardíaca/efeitos dos fármacos
Masculino
Camundongos
Camundongos Knockout
Antagonistas Muscarínicos/farmacologia
Contração Miocárdica/efeitos dos fármacos
Fisostigmina/farmacologia
Receptor Muscarínico M2/antagonistas & inibidores
Receptor Muscarínico M3/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenergic beta-1 Receptor Antagonists); 0 (Cholinesterase Inhibitors); 0 (Ganglionic Stimulants); 0 (Muscarinic Antagonists); 0 (Receptor, Muscarinic M2); 0 (Receptor, Muscarinic M3); 0 (Receptors, Adrenergic, beta-1); 50VV3VW0TI (Atenolol); 54-77-3 (Dimethylphenylpiperazinium Iodide); 7C0697DR9I (Atropine); 9U1VM840SP (Physostigmine)
[Em] Mês de entrada:1310
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130307
[St] Status:MEDLINE


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[PMID]:23407109
[Au] Autor:Lesko S; Wessler I; Gäbel G; Petto C; Pfannkuche H
[Ad] Endereço:Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
[Ti] Título:Cholinergic modulation of epithelial integrity in the proximal colon of pigs.
[So] Source:Cells Tissues Organs;197(5):411-20, 2013.
[Is] ISSN:1422-6421
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Within the gut, acetylcholine (ACh) is synthesised by enteric neurons, as well as by 'non-neuronal' epithelial cells. In studies of non-intestinal epithelia, ACh was involved in the generation of an intact epithelial barrier. In the present study, primary cultured porcine colonocytes were used to determine whether treatment with exogenous ACh or expression of endogenous epithelium-derived ACh may modulate epithelial tightness in the gastrointestinal tract. METHODS: Piglet colonocytes were cultured on filter membranes for 8 days. The tightness of the growing epithelial cell layer was evaluated by measuring transepithelial electrical resistance (TEER). To determine whether ACh modulates the tightness of the cell layer, cells were treated with cholinergic, muscarinic and/or nicotinic agonists and antagonists. Choline acetyltransferase (ChAT), cholinergic receptors and ACh were determined by immunohistochemistry, RT-PCR and HPLC, respectively. RESULTS: Application of the cholinergic agonist carbachol (10 µm) and the muscarinic agonist oxotremorine (10 µM) resulted in significantly higher TEER values compared to controls. The effect was completely inhibited by the muscarinic antagonist atropine. Application of atropine alone (without any agonist) led to significantly lower TEER values compared to controls. Synthesis of ACh by epithelial cells was proven by detection of muscarinic and nicotinic receptor mRNAs, immunohistochemical detection of ChAT and detection of ACh by HPLC. CONCLUSION: ACh is strongly involved in the regulation of epithelial tightness in the proximal colon of pigs via muscarinic pathways. Non-neuronal ACh seems to be of particular importance for epithelial cells forming a tight barrier.
[Mh] Termos MeSH primário: Colinérgicos/farmacologia
Colo/metabolismo
Mucosa Intestinal/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Colina O-Acetiltransferase/metabolismo
Colo/citologia
Colo/efeitos dos fármacos
Iodeto de Dimetilfenilpiperazina/farmacologia
Impedância Elétrica
Enterócitos/citologia
Enterócitos/efeitos dos fármacos
Enterócitos/enzimologia
Feminino
Imuno-Histoquímica
Mucosa Intestinal/citologia
Mucosa Intestinal/efeitos dos fármacos
Masculino
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Agonistas Nicotínicos/farmacologia
Ocludina/genética
Ocludina/metabolismo
Reação em Cadeia da Polimerase
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Receptores Colinérgicos/genética
Receptores Colinérgicos/metabolismo
Receptores Muscarínicos/genética
Receptores Muscarínicos/metabolismo
Transdução de Sinais/efeitos dos fármacos
Sus scrofa
Proteína da Zônula de Oclusão-1/genética
Proteína da Zônula de Oclusão-1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cholinergic Agents); 0 (Nicotinic Agonists); 0 (Occludin); 0 (RNA, Messenger); 0 (Receptors, Cholinergic); 0 (Receptors, Muscarinic); 0 (Zonula Occludens-1 Protein); 54-77-3 (Dimethylphenylpiperazinium Iodide); EC 2.3.1.6 (Choline O-Acetyltransferase)
[Em] Mês de entrada:1401
[Cu] Atualização por classe:130502
[Lr] Data última revisão:
130502
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130215
[St] Status:MEDLINE
[do] DOI:10.1159/000345437


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[PMID]:23335470
[Au] Autor:Zhong LR; Estes S; Artinian L; Rehder V
[Ad] Endereço:Biology Department, Georgia State University, Atlanta, GA 30302, USA.
[Ti] Título:Acetylcholine elongates neuronal growth cone filopodia via activation of nicotinic acetylcholine receptors.
[So] Source:Dev Neurobiol;73(7):487-501, 2013 Jul.
[Is] ISSN:1932-846X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In addition to acting as a classical neurotransmitter in synaptic transmission, acetylcholine (ACh) has been shown to play a role in axonal growth and growth cone guidance. What is not well understood is how ACh acts on growth cones to affect growth cone filopodia, structures known to be important for neuronal pathfinding. We addressed this question using an identified neuron (B5) from the buccal ganglion of the pond snail Helisoma trivolvis in cell culture. ACh treatment caused pronounced filopodial elongation within minutes, an effect that required calcium influx and resulted in the elevation of the intracellular calcium concentration ([Ca]i ). Whole-cell patch clamp recordings showed that ACh caused a reduction in input resistance, a depolarization of the membrane potential, and an increase in firing frequency in B5 neurons. These effects were mediated via the activation of nicotinic acetylcholine receptors (nAChRs), as the nAChR agonist dimethylphenylpiperazinium (DMPP) mimicked the effects of ACh on filopodial elongation, [Ca]i elevation, and changes in electrical activity. Moreover, the nAChR antagonist tubucurarine blocked all DMPP-induced effects. Lastly, ACh acted locally at the growth cone, because growth cones that were physically isolated from their parent neuron responded to ACh by filopodial elongation with a similar time course as growth cones that remained connected to their parent neuron. Our data revealed a critical role for ACh as a modulator of growth cone filopodial dynamics. ACh signaling was mediated via nAChRs and resulted in Ca influx, which, in turn, caused filopodial elongation.
[Mh] Termos MeSH primário: Acetilcolina/fisiologia
Cones de Crescimento/fisiologia
Neurônios/fisiologia
Pseudópodes/metabolismo
Receptores Nicotínicos/metabolismo
[Mh] Termos MeSH secundário: Acetilcolina/farmacologia
Animais
Células Cultivadas
Iodeto de Dimetilfenilpiperazina/farmacologia
Relação Dose-Resposta a Droga
Cones de Crescimento/efeitos dos fármacos
Helix (caramujos)
Neurônios/efeitos dos fármacos
Agonistas Nicotínicos/farmacologia
Pseudópodes/efeitos dos fármacos
Pseudópodes/fisiologia
Receptores Nicotínicos/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Nicotinic Agonists); 0 (Receptors, Nicotinic); 54-77-3 (Dimethylphenylpiperazinium Iodide); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1401
[Cu] Atualização por classe:130611
[Lr] Data última revisão:
130611
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130122
[St] Status:MEDLINE
[do] DOI:10.1002/dneu.22071



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