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Pesquisa : D06.472.699.327.935.524 [Categoria DeCS]
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[PMID]:26593415
[Au] Autor:Shpakov AO; Derkach KV; Shpakova EA
[Ad] Endereço:Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia. alex_shpakov@list.ru.
[Ti] Título:Regulation of the Melanocortin-Sensitive Adenylate Cyclase System by N-Acylated Peptide 71-82 of Type 4 Melanocortin Receptor.
[So] Source:Bull Exp Biol Med;160(1):40-4, 2015 Nov.
[Is] ISSN:1573-8221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The peptides structurally corresponding in to cytoplasmic loops of G protein-coupled receptors (GPCR) are able to control functional activity of homologous receptors and the corresponding signaling pathways. Modification of these peptides with hydrophobic radicals enhances their biological activity due to penetration of lipophilic derivatives through the membrane and anchoring near their targets, GPCR. We synthesized an N-palmitoylated peptide Palm-Val-[Lys-Asn-Lys-Asn-Leu-His-Ser-Pro-(Nle)-Tyr-Phe-Phe71-82]-amide-Palm-Val-(71-82) structurally corresponding to cytoplasmic loop 1 of melanocortin 4 receptor (M4R). We found that in micromolar concentrations it very effectively suppresses stimulation of basal adenylate cyclase activity and basal level of GppNHp binding of heterotrimeric G proteins produced by THIQ and α-melanocyte stimulating hormone (α-MSH), agonists of M4R homologous to the peptide, in synaptosomal membranes of rat brain. The peptide Palm-Val-(71-82) also reduced, albeit to a significantly less extent, stimulation of adenylate cyclase and G-proteins by M3R agonist of γ-MSH, due to high homology of the peptide primary structure to M3R cytoplasmic loop 1. The synthesized peptide with activity of M4R/M3R antagonist can be used for the development of regulators of M4R and M3R and the corresponding biochemical and physiological processes.
[Mh] Termos MeSH primário: Receptor Tipo 4 de Melanocortina/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adenilil Ciclases/metabolismo
Sequência de Aminoácidos
Animais
Química Encefálica
Guanilil Imidodifosfato/farmacologia
Lipoilação
Masculino
Dados de Sequência Molecular
Fragmentos de Peptídeos/síntese química
Fragmentos de Peptídeos/farmacologia
Processamento de Proteína Pós-Traducional
Ratos
Ratos Wistar
Receptor Tipo 3 de Melanocortina/agonistas
Receptor Tipo 3 de Melanocortina/antagonistas & inibidores
Receptor Tipo 3 de Melanocortina/fisiologia
Receptor Tipo 4 de Melanocortina/agonistas
Receptor Tipo 4 de Melanocortina/química
Transdução de Sinais/fisiologia
Sinaptossomos/efeitos dos fármacos
Sinaptossomos/metabolismo
Tetra-Hidroisoquinolinas/farmacologia
Triazóis/farmacologia
alfa-MSH/farmacologia
gama-MSH/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (N-(1,2,3,4-tetrahydroisoquinolinium-3-ylcarbonyl)-1-(4-chlorobenzyl)-2-(4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl)-2-oxoethylamine); 0 (Peptide Fragments); 0 (Receptor, Melanocortin, Type 3); 0 (Receptor, Melanocortin, Type 4); 0 (Tetrahydroisoquinolines); 0 (Triazoles); 0 (gamma-MSH); 34273-04-6 (Guanylyl Imidodiphosphate); 581-05-5 (alpha-MSH); EC 4.6.1.1 (Adenylyl Cyclases)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:151207
[Lr] Data última revisão:
151207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151124
[St] Status:MEDLINE
[do] DOI:10.1007/s10517-015-3093-4


  2 / 97 MEDLINE  
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[PMID]:26300254
[Au] Autor:Jiang JP; Fu Y; Hu FJ; Hong YG
[Ad] Endereço:College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental and Neuro Biology, Fuzhou 350117, China. jjp@fjnu.edu.cn.
[Ti] Título:[Activation of spinal MrgC receptors inhibits hyperalgesia in rats].
[So] Source:Sheng Li Xue Bao;67(4):413-22, 2015 Aug 25.
[Is] ISSN:0371-0874
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:This study was aimed to investigate the mechanisms of the modulation effect of activation of spinal Mas-related gene C (MrgC) receptors on hyperalgesia induced by intraplantar (i.pl.) injection of (Tyr6)-γ2-MSH-6-12 (MSH) or complete Freund's adjuvant (CFA). Paw withdrawal latency test and immunohistochemistry were used to observe the effect of intrathecal (i.t.) administration of MSH or BAM8-22, two selective agonists of MrgC receptor, in hyperalgesia in rats. The results showed that i.t. administration of MSH inhibited acute hyperalgesic response induced by i.pl. application of MSH, while did not change thermal nociceptive threshold in naïve rats. The i.t. administration of MSH also attenuated CFA-induced inflammatory hyperalgesia. However, i.t. administration of the µ-opioid receptor (MOR) antagonist CTAP blocked the induction of delayed anti-hyperalgesia by MSH. The i.t. injection of BAM8-22 at a dose of 30 nmol evidently reduced the number of CFA-evoked nitric oxide synthase (NOS)-positive neurons and the expression of calcitonin gene-related peptide (CGRP)-immunoreactivity positive nerve fibers at L3-L5 segments of the spinal cord. These results suggest that the activation of MrgC receptor in CFA-induced inflammation reduces inflammatory hyperalgesia through inactivation of NOS neurons and down-regulation of CGRP expressions, and generates delayed but long-lasting anti-nociception through the endogenous activation of MOR via indirect mechanisms. Agonists for MrgC receptors may, therefore, represent a new class of antihyperalgesics for treating inflammatory pain because of the highly specific expression of their targets.
[Mh] Termos MeSH primário: Hiperalgesia/tratamento farmacológico
Receptores Acoplados a Proteínas-G/metabolismo
Medula Espinal/metabolismo
[Mh] Termos MeSH secundário: Animais
Regulação para Baixo
Adjuvante de Freund/farmacologia
Inflamação/metabolismo
Injeções Espinhais
Medição da Dor
Fragmentos de Peptídeos/farmacologia
Ratos
gama-MSH/farmacologia
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mrgprc protein, rat); 0 (Peptide Fragments); 0 (Receptors, G-Protein-Coupled); 0 (bovine adrenal medulla 8-22); 0 (gamma-MSH); 0 (gamma2-MSH (6-12), Tyr(6)-); 9007-81-2 (Freund's Adjuvant)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:150824
[Lr] Data última revisão:
150824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150825
[St] Status:MEDLINE


  3 / 97 MEDLINE  
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[PMID]:26145509
[Au] Autor:Zhou L; Yang Q; He C; Wei C; Yang Y; Dong S
[Ad] Endereço:The Core Laboratory of the First Affiliated Hospital, Lanzhou University, 1 Donggang West Road, Lanzhou 730000, China; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou 730000, China. Electronic address: zhoulx@lzu.edu.cn.
[Ti] Título:Interaction of endokinin A/B and (Mpa(6))-γ2-MSH-6-12 in pain regulation in mice.
[So] Source:Neuropeptides;53:79-84, 2015 Oct.
[Is] ISSN:1532-2785
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The present study focused on the interactive effects of (Mpa(6))-γ2-MSH-6-12 (Mpa, spinal level) and endokinin A/B (EKA/B, supraspinal level) on pain regulation in mice. EKA/B (30 pmol) only weakened 100 pmol Mpa-induced hyperalgesia at 5 min, but could enhance it during 20-30 min. However, EKA/B (100 pmol) antagonized all dose levels of Mpa significantly at 5 min and blocked them completely at 10 min. EKA/B (3 nmol) co-injected with Mpa presented marked analgesia at 5 min and enduring hyperalgesia within 20-60 min. To investigate the underlying mechanisms between Mpa and EKA/B, SR140333B and SR142801 (NK1 and NK3 receptor antagonists, respectively) were utilized. SR140333B had no influence on Mpa, while SR142801 potentiated it during 20-30 min. Whereas, SR140333B and SR142801 could block the co-administration of Mpa and EKA/B (30 pmol) separately at 5 min and 30 min. These phenomena might attribute to that these two antagonists promoted the antagonism of EKA/B (30 pmol) at the early stage, while antagonized EKA/B preferentially in the latter period. SR140333B weakened the analgesia of EKA/B (3 nmol), but produced no effect on Mpa. However, SR140333B failed to affect the co-injection of Mpa and EKA/B, which implied that EKA/B cooperated with Mpa prior to SR140333B. These results could potentially help to better understand the interaction of NK and MrgC receptors in pain regulation in mice.
[Mh] Termos MeSH primário: Hiperalgesia/tratamento farmacológico
Neurocinina A/farmacologia
Neurocinina B/farmacologia
Dor/fisiopatologia
gama-MSH/antagonistas & inibidores
gama-MSH/farmacologia
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Hiperalgesia/induzido quimicamente
Injeções Intraventriculares
Injeções Espinhais
Masculino
Camundongos
Antagonistas do Receptor de Neuroquinina-1/farmacologia
Medição da Dor/efeitos dos fármacos
Piperidinas/farmacologia
Receptores da Neurocinina-3/antagonistas & inibidores
Tropanos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Neurokinin-1 Receptor Antagonists); 0 (Piperidines); 0 (Receptors, Neurokinin-3); 0 (SR 142801); 0 (SR140333B); 0 (Tropanes); 0 (gamma-MSH); 86933-74-6 (Neurokinin A); 86933-75-7 (Neurokinin B)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:151013
[Lr] Data última revisão:
151013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150707
[St] Status:MEDLINE


  4 / 97 MEDLINE  
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[PMID]:25697006
[Au] Autor:Shpakov AO; Shpakova EA; Tarasenko II; Derkach KV
[Ti] Título:[N-palmitoylated peptide 232-245 of rat type 4 melanocortin receptor possessing agonistic activity].
[So] Source:Tsitologiia;56(8):604-11, 2014.
[Is] ISSN:0041-3771
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Melanocortin receptors of the type 4 (M4R) play a key role in the regulation of feeding behavior, neuroendocrine functions, and energy metabolism. The alterations in their functional activity induce obesity, metabolic syndrome, depression, and mental disorders, which makes the search of selective regulators of M4R to be one of the actual problems of molecular endocrinology. Promising for the development of such regulators is to design peptides corresponding to functionally important regions of M4R. The purpose of this study was to study the influence of synthesized N-palmitoylated peptide Palm-Thr-Gly-Thr-Ile-Arg-Gln-Gly-Ala-Asn-(Nle)-Lys-Gly-Ala-Ile232-245-amide (Palm-232-245) structurally corresponding to the C-terminal half of the third intracellular loop (ICL-3) of rat M4R on functional activity of adenylyl cyclase signaling system (ACSS) in the fractions of synaptosomal membranes isolated from the brains of male rats. It has been shown that, at a concentration of 10(-7) M and higher, Palm-232-245 stimulates the basal activity of adenylyl cyclase (AC) in the synaptosomal membranes and increases the basal level of GTP binding with the EC50 values of 71 and 267 nM, respectively. Under the combined action of low concentrations of the peptide (10(-7)-10(-6) M) and M4R agonists, α-melanocyte-stimulating hormone (α-MSH) and THIQ (10(-7) M), we observed an additivi stimulatory effect on AC, which disappeared when the peptide concentration was increased to 10(-4)-10(-3) M. In the synaptosomal membranes preincubated with 10(-5) M peptide, the maximum stimulatory effect of M4R agonists on AC activity was lower than that in controls, and EC50 values for this effect, on the contrary, increased. In the case of combined action of the peptide and hormones (γ-MSH, serotonin, PACAP-38) that activate AC via the other receptors, the additivity of their stimulating effects on the ACSS persisted throughout the range of peptide concentrations. The effect of the peptide was not observed in myocardial and testicular membranes no in which there is M4R homologous to the peptide. Thus, N-palmitoylated peptide Palm-232-245 specifically activates the ACSS in the rat brain by acting as intracellular M4R agonist. This may be used to create drugs regulating brain melanocortin system and physiological processes that depend on it.
[Mh] Termos MeSH primário: Adenilil Ciclases/metabolismo
Encéfalo/efeitos dos fármacos
Peptídeos/farmacologia
Receptor Tipo 4 de Melanocortina/agonistas
Sinaptossomos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Encéfalo/metabolismo
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Guanosina Trifosfato/metabolismo
Lipoilação
Masculino
Dados de Sequência Molecular
Miocárdio/química
Especificidade de Órgãos
Peptídeos/síntese química
Peptídeos/química
Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Ratos
Ratos Wistar
Receptor Tipo 4 de Melanocortina/metabolismo
Serotonina/farmacologia
Transdução de Sinais
Relação Estrutura-Atividade
Sinaptossomos/metabolismo
Testículo/química
Testículo/efeitos dos fármacos
Tetra-Hidroisoquinolinas/farmacologia
Triazóis/farmacologia
alfa-MSH/farmacologia
gama-MSH/farmacologia
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (N-(1,2,3,4-tetrahydroisoquinolinium-3-ylcarbonyl)-1-(4-chlorobenzyl)-2-(4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl)-2-oxoethylamine); 0 (Peptides); 0 (Pituitary Adenylate Cyclase-Activating Polypeptide); 0 (Receptor, Melanocortin, Type 4); 0 (Tetrahydroisoquinolines); 0 (Triazoles); 0 (gamma-MSH); 333DO1RDJY (Serotonin); 581-05-5 (alpha-MSH); 86-01-1 (Guanosine Triphosphate); EC 4.6.1.1 (Adenylyl Cyclases)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150221
[St] Status:MEDLINE


  5 / 97 MEDLINE  
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[PMID]:25509773
[Au] Autor:Jiang W; Liu Y; Yang L; Xu W; Liu S; Zhang D; Chen X; Wang H
[Ti] Título:[Biomechanical comparative study on proximal femoral locking plate and Gamma3 for treatment of stable intertrochanteric fracture].
[So] Source:Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi;28(9):1096-9, 2014 Sep.
[Is] ISSN:1002-1892
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To compare the biomechanical properties between the proximal femoral locking plate and Gamma3 for fixing stable intertrochanteric fracture so as to provide a theoretical basis for selecting internal fixation in the clinical application. METHODS: Five pairs of antiseptic femur specimens were selected. Specimens of each pair of matching were randomly divided into groups A and B (n=5). All specimens were made the intertrochanteric fracture of 31A1.1 type according to AO/Association for the Study of Internal Fixation (AO/ASIF) classification. Fracture was fixed with Gamma3 in group A and with proximal femoral locking plate in group B. The axial compression, destruction, and torsion tests were carried out on the mechanical testing machine. RESULTS: Axial compression test: The load-displacement curve of groups A and B was basically a straight line; axial stiffness of groups A and B was (621.00 ± 36.48) N/mm and (542.55 ± 46.94) N/mm respectively, showing significant difference (t = 3.648, P = 0.036). Destruction test: The maximum yield load of groups A and B was (4,394.82 ± 450.37) N and (2,987.54 ± 112.14) N respectively, showing significant difference (t = 5.433, P = -0.032). After loading maximum yield load, femoral fracture occurred again, and internal fixation and bone interface loosening were observed in group A; bending and breaking of proximal locking screw for internal fixation were found in group B, but loosening of internal fixation and bone interface was more obvious in group A than in group B. Torsion test: The torque of specimens in 2 groups increased with the increase of torsion angle (P < 0.05), the torque corresponding to the torsion angle in group B was larger than that in group A, but the difference was not significant (P > 0.05). The torsional stiffness of groups A and B was (1.78 ± 0.16) N·mm/deg and (2.01 ± 0.08) N·mm/deg respectively, showing no significant difference (t = -3.833, P = 0.162). CONCLUSION: Proximal femoral locking plate and Gamma3 in the treatment of stable intertrochanteric fracture have good biomechanical properties, which can meet the requirements of minimal invasion, strong internal fixation, and early activity.
[Mh] Termos MeSH primário: Placas Ósseas
Parafusos Ósseos
Fixação Interna de Fraturas/instrumentação
Fraturas do Quadril/cirurgia
[Mh] Termos MeSH secundário: Fenômenos Biomecânicos
Fraturas do Fêmur
Fêmur
Fixação Interna de Fraturas/métodos
Fraturas do Quadril/fisiopatologia
Resultado do Tratamento
gama-MSH
[Pt] Tipo de publicação:COMPARATIVE STUDY; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (gamma-MSH)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:141215
[Lr] Data última revisão:
141215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141217
[St] Status:MEDLINE


  6 / 97 MEDLINE  
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[PMID]:23871693
[Au] Autor:Cope G; Kaushik G; O'Sullivan SM; Healy V
[Ad] Endereço:Department of Physiology, University College Cork, Ireland.
[Ti] Título:Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells.
[So] Source:Peptides;47:54-9, 2013 Sep.
[Is] ISSN:1873-5169
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gamma(2)-melanocyte-stimulating hormone (γ2MSH) is a peptide hormone released by the pituitary gland which is thought to act directly on the renal inner medulla to promote increased sodium excretion into urine (natriuresis). The aim of this study was to determine if a stable analog, [Nle(3), D-Phe(6)]-γ2MSH (NDP-γ2MSH), of the native peptide regulated the activity, expression and cellular localization of epithelial sodium channel (ENaC) in a murine inner medullary collecting duct (mIMCD-3) cell line. Our results indicate that expression of the γ2MSH receptor, melanocortin receptor 3 receptor (MC3R), is up-regulated by culturing the cells in media with an increased osmolality (∼400mOsm/kg). Furthermore, stimulation of cAMP signaling and sodium transport by 1nM NDP-γ2MSH occurs only in cells cultured in the high osmolality media. Finally, treatment of mIMCD-3 cells cultured in high osmolality medium for 1h with 1nM NDP-γ2MSH causes a reduction in expression of serum- and glucocorticoid-induced kinase (sgk1) and a reduction in expression and cell surface abundance of the alpha subunit of ENaC. Collectively, this data suggest that γ2MSH directly regulates both ENaC expression and cellular localization in the inner medulla to exert its natriuretic effect.
[Mh] Termos MeSH primário: Células Epiteliais/metabolismo
Canais Epiteliais de Sódio/genética
Túbulos Renais Coletores/metabolismo
gama-MSH/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Meios de Cultura
AMP Cíclico/metabolismo
Células Epiteliais/citologia
Células Epiteliais/efeitos dos fármacos
Canais Epiteliais de Sódio/metabolismo
Regulação da Expressão Gênica
Proteínas Imediatamente Precoces/genética
Proteínas Imediatamente Precoces/metabolismo
Transporte de Íons
Túbulos Renais Coletores/citologia
Túbulos Renais Coletores/efeitos dos fármacos
Camundongos
Natriurese/genética
Concentração Osmolar
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Receptor Tipo 3 de Melanocortina/genética
Receptor Tipo 3 de Melanocortina/metabolismo
Transdução de Sinais
Sódio/metabolismo
alfa-MSH/análogos & derivados
alfa-MSH/farmacologia
gama-MSH/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Culture Media); 0 (Epithelial Sodium Channels); 0 (Immediate-Early Proteins); 0 (Mc3r protein, mouse); 0 (Receptor, Melanocortin, Type 3); 0 (gamma-MSH); 581-05-5 (alpha-MSH); 75921-69-6 (MSH, 4-Nle-7-Phe-alpha-); 9NEZ333N27 (Sodium); E0399OZS9N (Cyclic AMP); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:130902
[Lr] Data última revisão:
130902
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130723
[St] Status:MEDLINE


  7 / 97 MEDLINE  
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Texto completo
[PMID]:23276279
[Au] Autor:Cai M; Stankova M; Muthu D; Mayorov A; Yang Z; Trivedi D; Cabello C; Hruby VJ
[Ad] Endereço:Department of Chemistry and Biochemistry, 1306 East University Boulevard, University of Arizona, Tucson, AZ 85721, USA.
[Ti] Título:An unusual conformation of γ-melanocyte-stimulating hormone analogues leads to a selective human melanocortin 1 receptor antagonist for targeting melanoma cells.
[So] Source:Biochemistry;52(4):752-64, 2013 Jan 29.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:γ-MSH (γ-melanocyte-stimulating hormone, H-Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly-OH), with its exquisite specificity and potency, has recently created much excitement as a drug lead. However, this peptide is like most peptides susceptible to proteolysis in vivo, which potentially decreases its beneficial activities. In our continued effort to design a proteolytically stable ligand with specific receptor binding, we have engineered peptides by cyclizing γ-MSH using a thioether bridge. A number of novel cyclic truncated γ-MSH analogues were designed and synthesized, in which a thioether bridge was incorporated between a cysteine side chain and an N-terminal bromoacyl group. One of these peptides, cyclo-[(CH(2))(3)CO-Gly(1)-His(2)-D-Phe(3)-Arg(4)-D-Trp(5)-Cys(S-)(6)]-Asp(7)-Arg(8)-Phe(9)-Gly(10)-NH(2), demonstrated potent antagonist activity and receptor selectivity for the human melanocortin 1 receptor (hMC1R) (IC(50) = 17 nM). This novel peptide is the most selective antagonist for the hMC1R to date. Further pharmacological studies have shown that this peptide can specifically target melanoma cells. The nuclear magnetic resonance analysis of this peptide in a membrane-like environment revealed a new turn structure, specific to the hMC1R antagonist, at the C-terminus, where the side chain and backbone conformation of D-Trp(5) and Phe(9) of the peptide contribute to hMC1R selectivity. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Melanoma/tratamento farmacológico
Peptídeos Cíclicos/farmacologia
Receptor Tipo 1 de Melanocortina/antagonistas & inibidores
gama-MSH/farmacologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Linhagem Celular Tumoral/efeitos dos fármacos
Seres Humanos
Ligações de Hidrogênio
Concentração Inibidora 50
Hormônios Estimuladores de Melanócitos/química
Hormônios Estimuladores de Melanócitos/farmacologia
Simulação de Dinâmica Molecular
Terapia de Alvo Molecular
Ligação Proteica
Estrutura Secundária de Proteína
Receptor Tipo 1 de Melanocortina/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Peptides, Cyclic); 0 (Receptor, Melanocortin, Type 1); 0 (cyclo((CH2)3-Gly-His-D-Phe-Arg-D-Trp-Cys(S-))-Asp-Arg-Phe-Gly-NH2); 0 (gamma-MSH); 168482-23-3 (SHU 9119); 9002-79-3 (Melanocyte-Stimulating Hormones)
[Em] Mês de entrada:1303
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130102
[St] Status:MEDLINE
[do] DOI:10.1021/bi300723f


  8 / 97 MEDLINE  
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[PMID]:23106106
[Au] Autor:Cope G; Flanagan ET; Houghton BL; Walsh SA; Johns EJ; Healy V
[Ad] Endereço:Department of Physiology, University College Cork, Cork, Ireland.
[Ti] Título:[Nle3,d-Phe6 ]-γ2 -melanocyte-stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ2 -melanocyte-stimulating hormone in anaesthetized rats.
[So] Source:Clin Exp Pharmacol Physiol;40(1):5-12, 2013 Jan.
[Is] ISSN:1440-1681
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:The present study compared the cardiovascular and renal actions of γ(2) -melanocyte-stimulating hormone (γ(2) MSH) with those of the synthetic analogue [Nle(3) ,d-Phe(6) ]-γ(2) MSH (NDP-γ(2) MSH) and explored the effects of high dietary salt intake on the renal actions of NDP-γ(2) MSH. Both peptides were infused systemically (3-1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated rats fed either a normal (0.4% NaCl) or high-salt (4% NaCl; HS) diet. Mean arterial pressure (MAP), glomerular filtration rate (GFR), urinary sodium excretion (U(N) (a) V), urinary output (UV) and fractional sodium excretion were determined, as was expression of the melanocortin MC(3) receptor in inner medullary collecting duct (IMCD) epithelial cells. Both renal and systemic infusion of γ(2) MSH increased MAP by 23 ± 2% and 54 ± 4%, respectively, but equivalent doses of NDP-γ(2) MSH had no significant pressor effects. Both peptides had similar natriuretic and diuretic effects in rats fed a normal salt diet. However, NDP-γ(2) MSH increased U(N) (a) V and UV by two- to threefold in rats fed the normal salt diet and by six- to sevenfold in rats fed the HS diet. Furthermore, NDP-γ(2) MSH induced a 3.5-fold increase in GFR only in rats fed the HS diet. These renal effects of NDP-γ(2) MSH were not abolished by prior renal denervation. Rats fed the HS diet also exhibited a 4.5-fold increase in MC(3) receptor expression in IMCD epithelial cells. Intrarenal infusion of NDP-γ(2) MSH induced the natriuretic but not the cardiovascular effects exhibited by γ(2) MSH. The renal activities may be attributed to a direct binding of NDP-γ(2) MSH to MC(3) receptors expressed in IMCD cells, leading to a potent natriuretic effect that is independent of renal innervation.
[Mh] Termos MeSH primário: Sistema Cardiovascular/efeitos dos fármacos
Medula Renal/efeitos dos fármacos
Túbulos Renais Coletores/efeitos dos fármacos
gama-MSH/farmacologia
[Mh] Termos MeSH secundário: Animais
Pressão Arterial/efeitos dos fármacos
Sistema Cardiovascular/metabolismo
Denervação/métodos
Diuréticos/farmacologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Taxa de Filtração Glomerular/efeitos dos fármacos
Medula Renal/metabolismo
Túbulos Renais Coletores/metabolismo
Masculino
Natriuréticos/farmacologia
Ratos
Ratos Wistar
Receptor Tipo 3 de Melanocortina/metabolismo
Sais/metabolismo
Sódio/metabolismo
Cloreto de Sódio na Dieta/metabolismo
alfa-MSH/análogos & derivados
alfa-MSH/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Diuretics); 0 (Natriuretic Agents); 0 (Receptor, Melanocortin, Type 3); 0 (Salts); 0 (Sodium Chloride, Dietary); 0 (gamma-MSH); 581-05-5 (alpha-MSH); 75921-69-6 (MSH, 4-Nle-7-Phe-alpha-); 9NEZ333N27 (Sodium)
[Em] Mês de entrada:1309
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:121031
[St] Status:MEDLINE
[do] DOI:10.1111/1440-1681.12025


  9 / 97 MEDLINE  
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[PMID]:22760063
[Au] Autor:Honda K; Saneyasu T; Hasegawa S; Kamisoyama H
[Ad] Endereço:Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan. honda@tiger.kobe-u.ac.jp
[Ti] Título:A comparative study of the central effects of melanocortin peptides on food intake in broiler and layer chicks.
[So] Source:Peptides;37(1):13-7, 2012 Sep.
[Is] ISSN:1873-5169
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Broiler chicks eat more food than layer chicks. However, the causes of the difference in food intake in the neonatal period between these strains are not clear. In this study, we examined the involvement of proopiomelanocortin (POMC)-derived melanocortin peptides α-, ß- and γ-melanocyte-stimulating hormones (MSHs) in the difference in food intake between broiler and layer chicks. First, we compared the hypothalamic mRNA levels of POMC between these strains and found that there was no significant difference in these levels between broiler and layer chicks. Next, we examined the effects of central administration of MSHs on food intake in these strains. Central administration of α-MSH significantly suppressed food intake in both strains. Central administration of ß-MSH significantly suppressed food intake in layer chicks, but not in broiler chicks, while central administration of γ-MSH did not influence food intake in either strain. It is therefore likely that the absence of the anorexigenic effect of ß-MSH might be related to the increased food intake in broiler chicks.
[Mh] Termos MeSH primário: Apetite/efeitos dos fármacos
Galinhas/metabolismo
Ingestão de Energia/efeitos dos fármacos
alfa-MSH/fisiologia
beta-MSH/fisiologia
gama-MSH/fisiologia
[Mh] Termos MeSH secundário: Animais
Expressão Gênica
Hipotálamo/metabolismo
Masculino
Pró-Opiomelanocortina/genética
Pró-Opiomelanocortina/metabolismo
Receptor Tipo 4 de Melanocortina/genética
Receptor Tipo 4 de Melanocortina/metabolismo
alfa-MSH/farmacologia
beta-MSH/farmacologia
gama-MSH/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Receptor, Melanocortin, Type 4); 0 (beta-MSH); 0 (gamma-MSH); 581-05-5 (alpha-MSH); 66796-54-1 (Pro-Opiomelanocortin)
[Em] Mês de entrada:1301
[Cu] Atualização por classe:120824
[Lr] Data última revisão:
120824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120705
[St] Status:MEDLINE
[do] DOI:10.1016/j.peptides.2012.06.015


  10 / 97 MEDLINE  
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[PMID]:22471953
[Au] Autor:Kaneva MK; Kerrigan MJ; Grieco P; Curley GP; Locke IC; Getting SJ
[Ad] Endereço:School of Life Sciences, University of Westminster, London, UK.
[Ti] Título:Chondroprotective and anti-inflammatory role of melanocortin peptides in TNF-α activated human C-20/A4 chondrocytes.
[So] Source:Br J Pharmacol;167(1):67-79, 2012 Sep.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Melanocortin MC(1) and MC(3 ) receptors, mediate the anti-inflammatory effects of melanocortin peptides. Targeting these receptors could therefore lead to development of novel anti-inflammatory therapeutic agents. We investigated the expression of MC(1) and MC(3) receptors on chondrocytes and the role of α-melanocyte-stimulating hormone (α-MSH) and the selective MC(3) receptor agonist, [DTRP(8) ]-γ-MSH, in modulating production of inflammatory cytokines, tissue-destructive proteins and induction of apoptotic pathway(s) in the human chondrocytic C-20/A4 cells. EXPERIMENTAL APPROACH: Effects of α-MSH, [DTRP(8) ]-γ-MSH alone or in the presence of the MC(3/4) receptor antagonist, SHU9119, on TNF-α induced release of pro-inflammatory cytokines, MMPs, apoptotic pathway(s) and cell death in C-20/A4 chondrocytes were investigated, along with their effect on the release of the anti-inflammatory cytokine IL-10. KEY RESULTS: C-20/A4 chondrocytes expressed functionally active MC(1,3) receptors. α-MSH and [DTRP(8) ]-γ-MSH treatment, for 30 min before TNF-α stimulation, provided a time-and-bell-shaped concentration-dependent decrease in pro-inflammatory cytokines (IL-1ß, IL-6 and IL-8) release and increased release of the chondroprotective and anti-inflammatory cytokine, IL-10, whilst decreasing expression of MMP1, MMP3, MMP13 genes.α-MSH and [DTRP(8) ]-γ-MSH treatment also inhibited TNF-α-induced caspase-3/7 activation and chondrocyte death. The effects of [DTRP(8) ]-γ-MSH, but not α-MSH, were abolished by the MC(3/4) receptor antagonist, SHU9119. CONCLUSION AND IMPLICATIONS: Activation of MC(1) /MC(3) receptors in C-20/A4 chondrocytes down-regulated production of pro-inflammatory cytokines and cartilage-destroying proteinases, inhibited initiation of apoptotic pathways and promoted release of chondroprotective and anti-inflammatory cytokines. Developing small molecule agonists to MC(1) /MC(3) receptors could be a viable approach for developing chondroprotective and anti-inflammatory therapies in rheumatoid and osteoarthritis.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Condrócitos/efeitos dos fármacos
Hormônios Estimuladores de Melanócitos/farmacologia
Substâncias Protetoras/farmacologia
alfa-MSH/farmacologia
gama-MSH/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Caspase 3/metabolismo
Caspase 7/metabolismo
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Condrócitos/metabolismo
AMP Cíclico/metabolismo
Citocinas/metabolismo
Dinoprostona/metabolismo
Seres Humanos
Metaloproteinases da Matriz/metabolismo
Receptor Tipo 1 de Melanocortina/metabolismo
Receptor Tipo 3 de Melanocortina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (MC3R protein, human); 0 (Protective Agents); 0 (Receptor, Melanocortin, Type 1); 0 (Receptor, Melanocortin, Type 3); 0 (gamma-MSH); 168482-23-3 (SHU 9119); 581-05-5 (alpha-MSH); 9002-79-3 (Melanocyte-Stimulating Hormones); E0399OZS9N (Cyclic AMP); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 7); EC 3.4.24.- (Matrix Metalloproteinases); K7Q1JQR04M (Dinoprostone)
[Em] Mês de entrada:1301
[Cu] Atualização por classe:150225
[Lr] Data última revisão:
150225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120405
[St] Status:MEDLINE
[do] DOI:10.1111/j.1476-5381.2012.01968.x



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