Navegando por Palavras-chave "cAMP"

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    Effects of BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase, on human NADPH oxidase system from THP-1 cells
    (Elsevier B.V., 2007-07-12) Oliveira-Junior, Edgar Borges de; Thomazzi, Sara Maria; Relider, Jussara; Antunes, Edson; Condino-Neto, Antonio; Universidade Federal de São Paulo (UNIFESP); Univ Fed Sergipe; Universidade Estadual de Campinas (UNICAMP); Universidade de São Paulo (USP)
    We investigated the effects of the 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) on the NADPH oxidase activity, gp91(phox) gene expression, cyclic guanosine-3',5-monophosphate (cGMP) and cyclic adenosine-3',5'-monophosphate (cAMP) levels in the human myelomonocytic THP-1 cell line. THP-1 cells treated with BAY 41-2272 (0.3-10 mu M) for 48 h significantly increased the superoxide anion (O-2(center dot-)) release. This increase was not affected when cells were pre-treated with the specific cGMP-phosphodiesterase inhibitor zaprinast, the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (ODQ), the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl) adenine (SQ 22,536) or the nitric oxide synthase inhibitor N-omega-nitro-1-arginine methyl ester (I-NAME). in addition, BAY 41-2272 (3 and 10 mu M; 48 h) was able to increase gp91(phox) gene expression on THP-1 cells. the pre-treatment with zaprinast, 3-isobutyl-L-methyl-xanthine (IBMX; 0.5 mM), ODQ, SQ 22,536 or l-NAME caused no additional effect on the expression of gp91(phox) evoked by BAY 41-2272. Treatment of THP-1 cells with BAY 41-2272 caused a significant increase in cGMP and cAMP levels. Our findings show that BAY 41-2272 caused a significant increase on the O-2(center dot-) release and gp91(phox) gene expression by THP-1 cells, and an elevation of intracellular cGMP and cAMP levels. However, we could not detect a clear correlation between both O-2(center dot-) release and gp91(phox) gene expression with activation of cGMP and cAMP signaling pathways. (c) 2007 Elsevier B.V. All rights reserved.
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    Novel model for calcium paradox in sympathetic transmission of smooth muscles: Role of cyclic AMP pathway
    (Churchill Livingstone, 2013-09-01) Bergantin, Leandro Bueno [UNIFESP]; Souza, Claudio Fontes [UNIFESP]; Ferreira, Regiane Miranda [UNIFESP]; Smaili, Soraya Soubhi [UNIFESP]; Jurkiewicz, Neide Hyppolito [UNIFESP]; Caricati-Neto, Afonso [UNIFESP]; Jurkiewicz, Aron [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    It is well established that reduction of Ca2+ influx through L-type voltage-dependent Ca2+ channel (L-type VDCC), or increase of cytosolic cAMP concentration ([cAMP]c), inhibit contractile activity of smooth muscles in response to transmitters released from sympathetic nerves. Surprisingly, in this work we observed that simultaneous administration of L-type VDCC blocker (verapamil) and [cAMP]c enhancers (rolipram, IBMX and forskolin) potentiated purinergic contractions evoked by electrical field stimulation of rat vas deferens, instead of inhibiting them. These results, including its role in sympathetic transmission, can be considered as a calcium paradox. On the other hand, this potentiation was prevented by reduction of [cAMP]c by inhibition of adenylyl cyclase (SQ 22536) or depletion of Ca2+ storage of sarco-endoplasmic reticulum by blockade of Ca2+ reuptake (thapsigargin). in addition, cytosolic concentration ([Ca2+](c)) evaluated by fluorescence microscopy in rat adrenal medullary slices was significantly reduced by verapamil or rolipram. in contrast, simultaneous incubation of adrenal slices with these compounds significantly increased [Ca2+](c). This effect was prevented by thapsigargin. Thus, a reduction of [Ca2+](c) due to blockade of Ca2+ influx through L-type VDCC could stimulate adenylyl cyclase activity increasing [cAMP]c thereby stimulating Ca2+ release from endoplasmic reticulum, resulting in augmented transmitter release in sympathetic nerves and contraction. (C) 2013 Elsevier B.V. All rights reserved.
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    Skeletal muscle expresses the extracellular cyclic AMP-adenosine pathway
    (Nature Publishing Group, 2008-03-01) Chiavegatti, Tiago [UNIFESP]; Costa, V. L. [UNIFESP]; Araujo, M. S. [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background and purpose: cAMP is a key intracellular signalling molecule that regulates multiple processes of the vertebrate skeletal muscle. We have shown that cAMP can be actively pumped out from the skeletal muscle cell. Since in other tissues, cAMP efflux had been associated with extracellular generation of adenosine, in the present study we have assessed the fate of interstitial cAMP and the existence of an extracellular cAMP-adenosine signalling pathway in skeletal muscle.Experimental approach: cAMP efflux and/or its extracellular degradation were analysed by incubating rat cultured skeletal muscle with exogenous cAMP, forskolin or isoprenaline. cAMP and its metabolites were quantified by radioassay or HPLC, respectively.Key results: Incubation of cells with exogenous cAMP was followed by interstitial accumulation of 5'-AMP and adenosine, a phenomenon inhibited by selective inhibitors of ecto-phosphodiesterase ( DPSPX) and ecto-nucleotidase (AMPCP). Activation of adenylyl cyclase (AC) in cultured cells with forskolin or isoprenaline increased cAMP efflux and extracellular generation of 5'-AMP and adenosine. Extracellular cAMP-adenosine pathway was also observed after direct and receptor-dependent stimulation of AC in rat extensor muscle ex vivo. These events were attenuated by probenecid, an inhibitor of ATP binding cassette family transporters.Conclusions and implications: Our results show the existence of an extracellular biochemical cascade that converts cAMP into adenosine. the functional relevance of this extracellular signalling system may involve a feedback modulation of cellular response initiated by several G protein-coupled receptor ligands, amplifying cAMP influence to a paracrine mode, through its metabolite, adenosine.
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    Transcriptional regulatory elements in the rat bradykinin B-2 receptor gene
    (Elsevier B.V., 1996-06-01) Pesquero, João Bosco [UNIFESP]; Lindsey, Charles Julian [UNIFESP]; Paiva, Antonio Cechelli de Mattos [UNIFESP]; Ganten, Detlev; Bader, Michael; MAX DELBRUCK CTR MOLEC MED; Universidade Federal de São Paulo (UNIFESP)
    In an attempt to elucidate the mechanisms underlying the regulation of bradykinin B2 receptor gene expression, the molecular structure of the rat gene including the 5'-flanking region was characterized (J. Biol. Chem. 269: 26920-26925, 1994). in this study we show that the gene spans about 32 kb, including a long first intron of 25 kb. the promoter region drives reporter gene expression in NG108-15 neuroglioma cells, and its expression is upregulated by cAMP bradykinin, phorbol esters and by coexpression of an activated ras oncogene but not by dexamethasone.