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[PMID]:28632750
[Au] Autor:Custódio AH; de Lima MC; Vaccari B; Boer PA; Gontijo JAR
[Ad] Endereço:Department of Internal Medicine Faculty of Medical Science, State University of Campinas, Campinas, SP, Brazil.
[Ti] Título:Renal sodium handling and blood pressure changes in gestational protein-restricted offspring: Role of renal nerves and ganglia neurokinin expression.
[So] Source:PLoS One;12(6):e0179499, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Considering long-term changes in renal sodium handling and blood pressure in maternal protein-restricted (LP) offspring, we assumed that the development of LP hypertension results from abnormal dorsal root ganglia (DRG) neurokinin expression associated with impaired responsiveness of renal sensory receptors, promoting a reduced urinary excretion of sodium. The present study investigates whether increased blood pressure in protein-restricted offspring would be associated with changes in the DRG cells and in renal pelvic wall expression of NK1R, SP and CGRP when compared to NP offspring. In addition, we assessed the tubular sodium handling, estimated by creatinine and lithium clearances before and after bilateral renal denervation in conscious LP offspring relative to age-matched NP counterparts. METHODS: Dams received a normal (NP) or low-protein diet (LP) during their entire pregnancy period. Male NP or LP offspring underwent bilateral surgical renal denervation before the 8-week renal functional test and blood pressure measurements. Immunofluorescence staining in DRG cells was assessed in optical sections by confocal laser scanning microscope. RESULTS: The current data demonstrated a sustained rise in blood pressure associated with a decrease in fractional excretion of sodium (FENa) by reducing post-proximal tubule sodium rejection in 16-wk old LP rats relative to age-matched NP counterparts. According to this study, bilateral renal denervation attenuated blood pressure and increased FENa in LP offspring. Furthermore, an immunohistochemical analysis showed a reduced expression of SP and CGRP in DRGs of LP when compared with NP rats. Renal pelvis of LP rats did not show a strong CGRP expression related to NP rats, whereas there was no change in SP immunostaining. CONCLUSIONS: These observations raise the possibility that impaired DRG and pelvic neurokinin expression associated with responsiveness of renal sensory receptors in 16-wk old LP offspring are conducive to excess renal reabsorption of sodium and development of hypertension in this programmed model.
[Mh] Termos MeSH primário: Pressão Sanguínea/fisiologia
Dieta com Restrição de Proteínas
Gânglios Espinais/metabolismo
Pelve Renal/metabolismo
Neurocinina A/metabolismo
Sódio/metabolismo
[Mh] Termos MeSH secundário: Animais
Peptídeo Relacionado com Gene de Calcitonina/genética
Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Catecolaminas/análise
Creatinina/metabolismo
Feminino
Rim/fisiologia
Lítio/análise
Lítio/metabolismo
Masculino
Microscopia de Fluorescência
Neurocinina A/genética
Potássio/análise
Ratos
Ratos Wistar
Sódio/análise
Substância P/genética
Substância P/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Catecholamines); 33507-63-0 (Substance P); 83652-28-2 (Calcitonin Gene-Related Peptide); 86933-74-6 (Neurokinin A); 9FN79X2M3F (Lithium); 9NEZ333N27 (Sodium); AYI8EX34EU (Creatinine); RWP5GA015D (Potassium)
[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:170621
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179499


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[PMID]:28444173
[Au] Autor:Maguire CA; Song YB; Wu M; León S; Carroll RS; Alreja M; Kaiser UB; Navarro VM
[Ad] Endereço:Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
[Ti] Título:Tac1 Signaling Is Required for Sexual Maturation and Responsiveness of GnRH Neurons to Kisspeptin in the Male Mouse.
[So] Source:Endocrinology;158(7):2319-2329, 2017 Jul 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The tachykinins substance P (SP) and neurokinin A (Tac1) have emerged as novel regulators of kisspeptin/GnRH release. Recently, we documented that SP modulates reproductive function in the female mouse. Here, we extended this characterization to the male mouse. Tac1-/- male mice showed delayed puberty onset. They also presented significantly decreased expression levels of Pdyn (dynorphin) and Nos1 (nitric oxide synthase) in the mediobasal hypothalamus and elevated Gnrh1 levels. Unexpectedly, the response of Tac1-/- mice to central kisspeptin or senktide (neurokinin B receptor-agonist) administration was significantly decreased compared with controls, despite the preserved ability of GnRH neurons to stimulate luteinizing hormone release as demonstrated by central N-methyl-D-aspartate receptor administration, suggesting a deficit at the GnRH neuron level. Importantly, we demonstrated that kisspeptin receptor and SP receptor (NK1R) heterodimerize, indicating that changes in the SP tone could alter the responsiveness of GnRH neurons to kisspeptin. Finally, electrophysiological recordings from arcuate Kiss1 neurons showed that, although virtually all Kiss1 neurons responded to NKB and senktide, only half responded to an NK1R agonist and none to the neurokinin A receptor agonist at a 1-µM dose. In summary, we provide compelling evidence for a role of Tac1 in the control of reproductive function in the male mouse, suggesting a predominant central action that may involve a change in the balance of neural factors that control GnRH expression.
[Mh] Termos MeSH primário: Kisspeptinas/farmacologia
Neurocinina A/genética
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Maturidade Sexual/genética
[Mh] Termos MeSH secundário: Animais
Fenômenos Eletrofisiológicos/efeitos dos fármacos
Feminino
Hormônio Liberador de Gonadotropina/metabolismo
Células HEK293
Seres Humanos
Masculino
Camundongos
Camundongos Knockout
Neurocinina A/metabolismo
Neurônios/fisiologia
Maturidade Sexual/efeitos dos fármacos
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Kisspeptins); 33515-09-2 (Gonadotropin-Releasing Hormone); 86933-74-6 (Neurokinin A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.1210/en.2016-1807


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[PMID]:28315588
[Au] Autor:Gajjar S; Patel BM
[Ad] Endereço:Institute of Pharmacy, Nirma University, Ahmedabad, India.
[Ti] Título:Neuromedin: An insight into its types, receptors and therapeutic opportunities.
[So] Source:Pharmacol Rep;69(3):438-447, 2017 Jun.
[Is] ISSN:1734-1140
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:Neuropeptides are small protein used by neurons in signal communications. Neuromedin U was the first neuropeptide discovered from the porcine spinal and showed its potent constricting activities on uterus hence was entitled with neuromedin U. Following neuromedin U another of its isoform was discovered neuromedin S which was observed in suprachiasmatic nucleus hence was entitled neuromedin S. Neuromedin K and neuromedin L are of kanassin class which belong to tachykinin family. Bombesin family consists of neuromedin B and neuromedin C. All these different neuromedins have various physiological roles like constrictive effects on the smooth muscles, control of blood pressure, pain sensations, hunger, bone metastasis and release and regulation of hormones. Over the years various newer physiological roles have been observed thus opening ways for various novel therapeutic treatments. This review aims to provide an overview of important different types of neuromedin, their receptors, signal transduction mechanism and implications for various diseases.
[Mh] Termos MeSH primário: Neuropeptídeos/metabolismo
Receptores de Neurotransmissores/metabolismo
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Bombesina/metabolismo
Seres Humanos
Músculo Liso/metabolismo
Neurocinina A/metabolismo
Neurocinina B/metabolismo
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Neuropeptides); 0 (Receptors, Neurotransmitter); 0 (neuromedin S); 0 (neuromedin U receptor); 117505-80-3 (neuromedin U); 86933-74-6 (Neurokinin A); 86933-75-7 (Neurokinin B); PX9AZU7QPK (Bombesin)
[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:170319
[St] Status:MEDLINE


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[PMID]:27889808
[Au] Autor:Kullmann FA; Katofiasc M; Thor KB; Marson L
[Ad] Endereço:Department of Medicine, Renal Division, University of Pittsburgh, 3500 Terrace St, Scaife A1220, Pittsburgh, PA, 15261, USA.
[Ti] Título:Pharmacodynamic evaluation of Lys , MeLeu , Nle -NKA prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats.
[So] Source:Naunyn Schmiedebergs Arch Pharmacol;390(2):163-173, 2017 Feb.
[Is] ISSN:1432-1912
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The purpose of this study was to determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK receptor) agonist, Lys , MeLeu , Nle -NKA (LMN-NKA). Cystometry and colorectal pressure measurements were performed in urethane-anesthetized, intact, and acutely spinalized female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity. LMN-NKA (0.1-300 µg/kg) produced dose-dependent, rapid (<60 s), short-duration (<15 min) increases in bladder pressure. In intact rats, doses above 0.3-1 µg/kg induced urine release (voiding efficiency of ~70% at ≥1 µg/kg). In spinalized rats, urine release required higher doses (≥10 µg/kg) and was less efficient (30-50%). LMN-NKA (0.1-100 µg/kg) also produced dose-dependent increases in colorectal pressure. No tachyphylaxis was observed, and the responses were blocked by an NK receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious cardiorespiratory effects were noted. These results suggest that rapid-onset, short-duration, drug-induced voiding is possible in acute spinal and intact rats with intravenous administration of an NK receptor agonist. Future challenges remain in regard to finding alternative routes of administration that produce clinically significant voiding, multiple times per day, in animal models of chronic SCI.
[Mh] Termos MeSH primário: Colo/efeitos dos fármacos
Motilidade Gastrointestinal/efeitos dos fármacos
Contração Muscular/efeitos dos fármacos
Neurocinina A/análogos & derivados
Fragmentos de Peptídeos/farmacologia
Traumatismos da Medula Espinal/tratamento farmacológico
Bexiga Urinária/efeitos dos fármacos
Urodinâmica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Colo/inervação
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Estudos de Viabilidade
Feminino
Indóis/farmacologia
Neurocinina A/farmacologia
Piperidinas/farmacologia
Pressão
Ratos Sprague-Dawley
Receptores da Neurocinina-2/efeitos dos fármacos
Receptores da Neurocinina-2/metabolismo
Traumatismos da Medula Espinal/metabolismo
Traumatismos da Medula Espinal/fisiopatologia
Fatores de Tempo
Bexiga Urinária/inervação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GR 159897); 0 (Indoles); 0 (Peptide Fragments); 0 (Piperidines); 0 (Receptors, Neurokinin-2); 0 (neurokinin A (4-10), Lys(5)-MeLeu(9)-Nle(10)-); 86933-74-6 (Neurokinin A)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161128
[St] Status:MEDLINE
[do] DOI:10.1007/s00210-016-1317-4


  5 / 1719 MEDLINE  
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[PMID]:27638929
[Au] Autor:Ardill JE; Johnston BT; McCance DR; Eatock M
[Ad] Endereço:1 NET Group, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK.
[Ti] Título:Neurokinin A monitoring of response to interferon alpha in a patient with an advanced small bowel neuroendocrine tumour uncontrolled by somatostatin analogue therapy.
[So] Source:Ann Clin Biochem;54(2):297-301, 2017 Mar.
[Is] ISSN:1758-1001
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A 52-year-old lady presented with a history of occasional, severe abdominal cramps, postprandial diarrhoea and weight loss. After routine gastrointestinal investigations, she was diagnosed with irritable bowel syndrome. Over six months, she developed occasional facial flushing prompting assessment of neuroendocrine tumour markers. Urinary 5HIAA, 5HT, chromogranin A and neurokinin A were significantly elevated. Scans showed extensive hepatic metastases but did not show the location of a primary tumour. Somatostatin analogue therapy was commenced but despite increasing doses, symptoms increased and biomarkers rose dramatically. Interferon alpha was introduced concomitant with somatostatin analogue therapy. Biomarkers were monitored regularly. Within six months, symptoms abated and biomarkers reduced, continuing to fall over the next year, close to reference range. To manage side-effects of interferon alpha, dose was reduced from time to time. During these short periods, neurokinin A showed significant transient increases (75-150 ng/L) and carcinoid symptoms returned. For more than seven years, and with the co-operation of the patient, a balance was achieved between interferon alpha side-effects and disease control. Scans showed tumour load to be stable. The patient survived for 10 years post diagnosis. She chose to discontinue interferon alpha and received peptide receptor radiation therapy in her final year. Throughout, neurokinin A remained the most sensitive monitor of her disease progression.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Tumor Carcinoide/diagnóstico
Interferon-alfa/uso terapêutico
Neoplasias Intestinais/diagnóstico
Neoplasias Hepáticas/diagnóstico
Tumores Neuroendócrinos/diagnóstico
Neurocinina A/sangue
[Mh] Termos MeSH secundário: Antineoplásicos Hormonais/uso terapêutico
Tumor Carcinoide/sangue
Tumor Carcinoide/secundário
Tumor Carcinoide/terapia
Progressão da Doença
Monitoramento de Medicamentos
Feminino
Seres Humanos
Neoplasias Intestinais/sangue
Neoplasias Intestinais/patologia
Neoplasias Intestinais/terapia
Neoplasias Hepáticas/sangue
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/terapia
Meia-Idade
Estadiamento de Neoplasias
Tumores Neuroendócrinos/sangue
Tumores Neuroendócrinos/secundário
Tumores Neuroendócrinos/terapia
Somatostatina/química
Radioisótopos de Ítrio/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Biomarkers, Tumor); 0 (Interferon-alpha); 0 (Yttrium Radioisotopes); 51110-01-1 (Somatostatin); 86933-74-6 (Neurokinin A)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160918
[St] Status:MEDLINE
[do] DOI:10.1177/0004563216672492


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[PMID]:27704950
[Au] Autor:Fergani C; Mazzella L; Coolen LM; McCosh RB; Hardy SL; Newcomb N; Grachev P; Lehman MN; Goodman RL
[Ad] Endereço:Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Ce
[Ti] Título:Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?
[So] Source:Endocrinology;157(12):4829-4841, 2016 Dec.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is now general agreement that neurokinin B (NKB) acts via neurokinin-3-receptor (NK3R) to stimulate secretion of GnRH and LH in several species, including rats, mice, sheep, and humans. However, the roles of two other tachykinins, substance P (SP) and neurokinin A, which act primarily via NK1R and NK2R, respectively, are less clear. In rodents, these signaling pathways can stimulate LH release and substitute for NKB signaling; in humans, SP is colocalized with kisspeptin and NKB in the mediobasal hypothalamus. In this study, we examined the possible role of these tachykinins in control of the reproductive axis in sheep. Immunohistochemistry was used to describe the expression of SP and NK1R in the ovine diencephalon and determine whether these proteins are colocalized in kisspeptin or GnRH neurons. SP-containing cell bodies were largely confined to the arcuate nucleus, but NK1R-immunoreactivity was more widespread. However, there was very low coexpression of SP or NK1R in kisspeptin cells and none in GnRH neurons. We next determined the minimal effective dose of these three tachykinins that would stimulate LH secretion when administered into the third ventricle of ovary-intact anestrous sheep. A much lower dose of NKB (0.2 nmol) than of neurokinin A (2 nmol) or SP (10 nmol) consistently stimulated LH secretion. Moreover, the relative potency of these three neuropeptides parallels the relative selectivity of NK3R. Based on these anatomical and pharmacological data, we conclude that NKB-NK3R signaling is the primary pathway for the control of GnRH secretion by tachykinins in ewes.
[Mh] Termos MeSH primário: Hipotálamo/metabolismo
Hormônio Luteinizante/secreção
Neurônios/metabolismo
Receptores da Neurocinina-1/metabolismo
Substância P/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Feminino
Hormônio Liberador de Gonadotropina/metabolismo
Hipotálamo/efeitos dos fármacos
Imuno-Histoquímica
Kisspeptinas/metabolismo
Neurocinina A/administração & dosagem
Neurocinina B/administração & dosagem
Neurônios/efeitos dos fármacos
Ovinos
Transdução de Sinais/efeitos dos fármacos
Substância P/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Kisspeptins); 0 (Receptors, Neurokinin-1); 33507-63-0 (Substance P); 33515-09-2 (Gonadotropin-Releasing Hormone); 86933-74-6 (Neurokinin A); 86933-75-7 (Neurokinin B); 9002-67-9 (Luteinizing Hormone)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161006
[St] Status:MEDLINE


  7 / 1719 MEDLINE  
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[PMID]:27501920
[Au] Autor:Nederpelt I; Bleeker D; Tuijt B; IJzerman AP; Heitman LH
[Ad] Endereço:Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
[Ti] Título:Kinetic binding and activation profiles of endogenous tachykinins targeting the NK1 receptor.
[So] Source:Biochem Pharmacol;118:88-95, 2016 Oct 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ligand-receptor binding kinetics (i.e. association and dissociation rates) are emerging as important parameters for drug efficacy in vivo. Awareness of the kinetic behavior of endogenous ligands is pivotal, as drugs often have to compete with those. The binding kinetics of neurokinin 1 (NK1) receptor antagonists have been widely investigated while binding kinetics of endogenous tachykinins have hardly been reported, if at all. Therefore, the aim of this research was to investigate the binding kinetics of endogenous tachykinins and derivatives thereof and their role in the activation of the NK1 receptor. We determined the binding kinetics of seven tachykinins targeting the NK1 receptor. Dissociation rate constants (k ) ranged from 0.026±0.0029min (Sar ,Met(O ) -SP) to 0.21±0.015min (septide). Association rate constants (k ) were more diverse: substance P (SP) associated the fastest with a k value of 0.24±0.046nM min while neurokinin A (NKA) had the slowest association rate constant of 0.001±0.0002nM min . Kinetic binding parameters were highly correlated with potency and maximal response values determined in label-free impedance-based experiments on U-251 MG cells. Our research demonstrates large variations in binding kinetics of tachykinins which correlate to receptor activation. These findings provide new insights into the ligand-receptor interactions of tachykinins and underline the importance of measuring binding kinetics of both drug candidates and competing endogenous ligands.
[Mh] Termos MeSH primário: Proteínas do Tecido Nervoso/metabolismo
Neuroglia/metabolismo
Neurocinina A/metabolismo
Receptores da Neurocinina-1/metabolismo
Substância P/metabolismo
Taquicininas/metabolismo
[Mh] Termos MeSH secundário: Algoritmos
Animais
Astrocitoma/metabolismo
Ligação Competitiva
Células CHO
Linhagem Celular Tumoral
Cricetulus
Impedância Elétrica
Seres Humanos
Cinética
Ligantes
Proteínas do Tecido Nervoso/agonistas
Proteínas do Tecido Nervoso/genética
Neurocinina A/análogos & derivados
Neurocinina A/química
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
Ácido Pirrolidonocarboxílico/análogos & derivados
Ácido Pirrolidonocarboxílico/química
Ácido Pirrolidonocarboxílico/metabolismo
Ensaio Radioligante
Receptores da Neurocinina-1/agonistas
Receptores da Neurocinina-1/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Substância P/análogos & derivados
Substância P/química
Taquicininas/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Ligands); 0 (Nerve Tissue Proteins); 0 (Peptide Fragments); 0 (Receptors, Neurokinin-1); 0 (Recombinant Proteins); 0 (Tachykinins); 0 (hemokinin-1); 33507-63-0 (Substance P); 79775-19-2 (septide); 86933-74-6 (Neurokinin A); SZB83O1W42 (Pyrrolidonecarboxylic Acid)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160810
[St] Status:MEDLINE


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[PMID]:27456549
[Au] Autor:González-Santana A; Marrero-Hernández S; Dorta I; Hernández M; Pinto FM; Báez D; Bello AR; Candenas L; Almeida TA
[Ad] Endereço:Unidad de Farmacología, Facultad de Ciencias de la Salud, Universidad de La Laguna, Campus de Ofra s/n, Tenerife, Spain.
[Ti] Título:Altered expression of the tachykinins substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors in uterine leiomyomata.
[So] Source:Fertil Steril;106(6):1521-1529, 2016 Nov.
[Is] ISSN:1556-5653
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To study the expression levels of tachykinins and tachykinin receptors in uterine leiomyomas and matched myometrium. DESIGN: Laboratory study. SETTING: University research laboratories and academic hospital. PATIENT(S): Women undergoing hysterectomy for symptomatic leiomyomas. INTERVENTION(S): Quantitative polymerase chain reaction, immunohistochemistry and Western blot. MAIN OUTCOME MEASURE(S): Expression and tissue immunostaining of substance P, neurokinin A, hemokinin-1, neurokinin 1 receptor full-length (NK1R-Fl) and truncated (NK1R-Tr) isoforms, and neurokinin 2 receptor (NK2R) in paired samples of leiomyoma and adjacent normal myometrium. RESULT(S): TAC1 messenger RNA (mRNA) was significantly up-regulated in leiomyomas, whereas intense immunoreaction for the three peptides was particularly abundant in connective tissue cells. Differential regulation of TACR1 mRNA was observed, and at the protein level there was a significant increased expression of NK1R short isoform (NK1R-Tr). TACR2 mRNA was significantly up-regulated in leiomyomas, although levels of NK2R protein were similar in normal and tumor cells. CONCLUSION(S): These and our previous data demonstrate that the whole tachykinin system is differentially regulated in leiomyomas. The increased expression of NK1R-Tr might stimulate leiomyoma growth in a similar way to that observed in other steroid-dependent tumors.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Leiomioma/química
Neurocinina A/análise
Receptores da Neurocinina-1/análise
Receptores da Neurocinina-2/análise
Substância P/análise
Taquicininas/análise
Neoplasias Uterinas/química
[Mh] Termos MeSH secundário: Adulto
Biomarcadores Tumorais/genética
Western Blotting
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Leiomioma/genética
Leiomioma/patologia
Leiomioma/cirurgia
Meia-Idade
Neurocinina A/genética
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Receptores da Neurocinina-1/genética
Receptores da Neurocinina-2/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Substância P/genética
Taquicininas/genética
Neoplasias Uterinas/genética
Neoplasias Uterinas/patologia
Neoplasias Uterinas/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (RNA, Messenger); 0 (Receptors, Neurokinin-1); 0 (Receptors, Neurokinin-2); 0 (TAC4 protein, human); 0 (Tachykinins); 33507-63-0 (Substance P); 86933-74-6 (Neurokinin A)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160727
[St] Status:MEDLINE


  9 / 1719 MEDLINE  
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[PMID]:27199181
[Au] Autor:Kaczynska K; Jampolska M; Szereda-Przestaszewska M
[Ad] Endereço:Laboratory of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
[Ti] Título:The role of vagal pathway and NK1 and NK2 receptors in cardiovascular and respiratory effects of neurokinin A.
[So] Source:Clin Exp Pharmacol Physiol;43(9):818-24, 2016 Sep.
[Is] ISSN:1440-1681
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Neurokinin A (NKA) is a peptide neurotransmitter that participates in the regulation of breathing and the cardiovascular system. The purpose of the current study was to determine the cardiorespiratory pattern exerted by the systemic injection of NKA, to look at the contribution of neurokinin NK1 and NK2 receptors, and to establish the engagement of the vagal pathway in mediation of these responses. The effects of intravenous injections of NKA (50 µg/kg) were studied in anaesthetized, spontaneously breathing rats in the following experimental schemes: in neurally intact rats; and vagotomized at either midcervical or supranodosal level. Intravenous injections of NKA in the intact rats evoked sudden and short-lived increase in the respiratory rate concomitant with drop in tidal volume, followed by a prolonged depression, coupled with continuous augmentation of the tidal volume. Respiratory alterations were accompanied by transient tachycardia and prolonged hypotension. Midcervical vagotomy eliminated respiratory rate response and augmentation of tidal volume. Section of supranodosal vagi abrogated all respiratory reactions. NK2 receptor blockade abolished respiratory changes without affecting cardiovascular effects, whereas NK1 receptor blockade significantly reduced hypotension and increase in heart rate with no impact on the respiratory system. These results indicate that NKA induced changes in the breathing resulting from an excitation of the NK2 receptors on the vagal endings. A fall in blood pressure triggered by NKA occurs outside of the vagus nerve and is probably mediated via its direct action on vascular smooth muscles supplied with NK1 receptors.
[Mh] Termos MeSH primário: Pressão Sanguínea/efeitos dos fármacos
Neurocinina A/farmacologia
Receptores da Neurocinina-1/metabolismo
Receptores da Neurocinina-2/metabolismo
Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos
Nervo Vago/efeitos dos fármacos
Nervo Vago/metabolismo
[Mh] Termos MeSH secundário: Animais
Masculino
Antagonistas do Receptor de Neuroquinina-1/farmacologia
Ratos
Ratos Wistar
Receptores da Neurocinina-2/antagonistas & inibidores
Nervo Vago/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurokinin-1 Receptor Antagonists); 0 (Receptors, Neurokinin-1); 0 (Receptors, Neurokinin-2); 86933-74-6 (Neurokinin A)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160521
[St] Status:MEDLINE
[do] DOI:10.1111/1440-1681.12594


  10 / 1719 MEDLINE  
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[PMID]:27054429
[Au] Autor:Demir D; Cengiz N; Güven M; Bulduk O
[Ad] Endereço:*Department of Otorhinolaryngology†Department of Histology and Embryology, Sakarya University Faculty of Medicine, Sakarya, Turkey.
[Ti] Título:An Analysis of Neuropeptides at Nasal Contact Points of Patients With Secondary Headache.
[So] Source:J Craniofac Surg;27(3):e305-9, 2016 May.
[Is] ISSN:1536-3732
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: This prospective research study was designed to analyze the surgical outcomes and the intensity of substance P (SP), neurokinin A (NA), and calcitonin gene-related peptide (CGRP) in contact and noncontact nasal mucosa of patients with headache. METHODS: Twenty adults with secondary headache and correctible nasal obstruction were included in this study. The patients had nasal contact points between the nasal septum and the middle or inferior turbinates on nasal endoscopy and computed tomography scan. During surgical procedures, sample tissues were obtained from the nasal contact point and the noncontact area of the lateral nasal wall of these patients. Fluorescein staining intensity for antibodies against SP, NA, and CGRP was analyzed using image J software. Headaches were evaluated using a visual analog scale preoperatively and postoperatively. RESULTS: The differences between the preoperative and the postoperative 3rd month (P < 0.001) and 12th month (P < 0.001) visual analog scale scores were statistically significant. However, fluorescein staining intensity for SP (P = 0.631), NA (P = 0.546), and CGRP (P = 0.683) did not show statistically significant differences between the contact mucosa and the noncontact mucosa groups. CONCLUSIONS: Although in selected patients significant relief of headache can be obtained by surgery, there is no evidence from this study that SP, NA, and CGRP are responsible for the initiation of headache.
[Mh] Termos MeSH primário: Peptídeo Relacionado com Gene de Calcitonina/análise
Transtornos da Cefaleia Secundários/diagnóstico
Transtornos da Cefaleia Secundários/cirurgia
Mucosa Nasal/química
Obstrução Nasal/diagnóstico
Obstrução Nasal/cirurgia
Neurocinina A/análise
Substância P/análise
[Mh] Termos MeSH secundário: Adolescente
Adulto
Diagnóstico Diferencial
Endoscopia/métodos
Feminino
Seres Humanos
Masculino
Meia-Idade
Septo Nasal/química
Septo Nasal/cirurgia
Estudos Prospectivos
Conchas Nasais/química
Conchas Nasais/cirurgia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
33507-63-0 (Substance P); 83652-28-2 (Calcitonin Gene-Related Peptide); 86933-74-6 (Neurokinin A)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:160408
[St] Status:MEDLINE
[do] DOI:10.1097/SCS.0000000000002553



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