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Search Results: 1 - 5 of 5 matches for " Ardem Patapoutian "
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TRPV1 and TRPA1 Mediate Peripheral Nitric Oxide-Induced Nociception in Mice
Takashi Miyamoto,Adrienne E. Dubin,Matt J. Petrus,Ardem Patapoutian
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007596
Abstract: Nitric oxide (NO) can induce acute pain in humans and plays an important role in pain sensitization caused by inflammation and injury in animal models. There is evidence that NO acts both in the central nervous system via a cyclic GMP pathway and in the periphery on sensory neurons through unknown mechanisms. It has recently been suggested that TRPV1 and TRPA1, two polymodal ion channels that sense noxious stimuli impinging on peripheral nociceptors, are activated by NO in heterologous systems. Here, we investigate the relevance of this activation. We demonstrate that NO donors directly activate TRPV1 and TRPA1 in isolated inside-out patch recordings. Cultured primary sensory neurons display both TRPV1- and TRPA1-dependent responses to NO donors. BH4, an essential co-factor for NO production, causes activation of a subset of DRG neurons as assayed by calcium imaging, and this activation is at least partly dependent on nitric oxide synthase activity. We show that BH4-induced calcium influx is ablated in DRG neurons from TRPA1/TRPV1 double knockout mice, suggesting that production of endogenous levels of NO can activate these ion channels. In behavioral assays, peripheral NO-induced nociception is compromised when TRPV1 and TRPA1 are both ablated. These results provide genetic evidence that the peripheral nociceptive action of NO is mediated by both TRPV1 and TRPA1.
Single Residues in the Outer Pore of TRPV1 and TRPV3 Have Temperature-Dependent Conformations
Sung Eun Kim, Ardem Patapoutian, J?rg Grandl
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0059593
Abstract: Thermosensation is mediated by ion channels that are highly temperature-sensitive. Several members of the family of transient receptor potential (TRP) ion channels are activated by cold or hot temperatures and have been shown to function as temperature sensors in vivo. The molecular mechanism of temperature-sensitivity of these ion channels is not understood. A number of domains or even single amino acids that regulate temperature-sensitivity have been identified in several TRP channels. However, it is unclear what precise conformational changes occur upon temperature activation. Here, we used the cysteine accessibility method to probe temperature-dependent conformations of single amino acids in TRP channels. We screened over 50 amino acids in the predicted outer pore domains of the heat-activated ion channels TRPV1 and TRPV3. In both ion channels we found residues that have temperature-dependent accessibilities to the extracellular solvent. The identified residues are located within the second predicted extracellular pore loop. These residues are identical or proximal to residues that were shown to be specifically required for temperature-activation, but not chemical activation. Our data precisely locate conformational changes upon temperature-activation within the outer pore domain. Collectively, this suggests that these specific residues and the second predicted pore loop in general are crucial for the temperature-activation mechanism of these heat-activated thermoTRPs.
A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition
Matt Petrus, Andrea M Peier, Michael Bandell, Sun Hwang, Truc Huynh, Nicholas Olney, Tim Jegla, Ardem Patapoutian
Molecular Pain , 2007, DOI: 10.1186/1744-8069-3-40
Abstract: Sensory neurons of the dorsal root ganglia (DRGs) can detect environmental changes through projections in the skin. Among these primary afferent fibers, nociceptors play an important role in sensing noxious levels of mechanical and thermal stimuli [1]. One of the basic properties of nociceptors is their sensitization in response to injury and inflammation. For example, an innocuous stimulus such as a warm shower can become painful after sunburn, and this is called allodynia. Indeed, cold or mechanical allodynia are serious medical problems for patients suffering from neuropathic pain [2,3]. Hyperalgesia describes a similar condition, defined as an increased response to an already painful stimulus due to injury or inflammation.TRPV1, a member of the Transient Receptor Potential family of cation channels, is activated by heat, low pH, and capsaicin [4]. TRPV1 is expressed in nociceptors, and is sensitized in response to a variety of signal transduction pathways activated during inflammation [5,6]. TRPV1-deficient mice display negligible inflammatory heat hyperalgesia [7,8]. Much less is known about molecules involved in mechanical hyperalgesia.Originally characterized as a noxious cold-activated ion channel, TRPA1 is expressed in the same sensory neurons as TRPV1, and is activated directly by diverse reactive chemicals via covalent modification, and indirectly through G-protein coupled receptors [9-12]. TRPA1 is required to sense these noxious reactive chemicals in vivo; however, whether TRPA1 is required to sense acute noxious cold and mechanical stimulus is not yet settled [13-17]. Here, we examine the consequences of acute block of peripheral TRPA1 for pain transduction, focusing on mechanical hyperalgesia.To test if acute block of TRPA1 can modulate pain sensation, we sought a specific, efficient TRPA1 inhibitor. Ruthenium red, gadolinium, menthol, and camphor can inhibit TRPA1 activation, but also interact with other channels, including other TRP channels[18]. Us
A representa o como limita o – crítica de Deleuze à no o de diferen a ontológica em Heidegger = Representation as limitation - a critique of Deleuze to Heidegger's ontological difference
Mariza Ardem Scipioni Vial Ferronatto
Acta Scientiarum : Human and Social Sciences , 2010,
Abstract: Este artigo pretende colocar em discuss o a crítica de Deleuze a Heidegger, no que se refere ao problema da representa o. Para tanto, apresenta-se inicialmente a argumenta o deleuziana em torno daquilo que ele nomeia como a imagem dogmática do pensamento. A inten o é ressaltar os pontos que, segundo o filósofo francês, contaminam afilosofia da diferen a executada por Heidegger. Num segundo momento, aborda-se o tema da diferen a ontológica segundo a concep o do filósofo alem o. Exp em-se, ent o, argumentos que indicam possíveis inconsistências na crítica de Deleuze, que acusa Heidegger de livrar-se dos pressupostos objetivos à custa de dar-se pressupostos subjetivos. This article intends to discuss the critique of Deleuze to Heidegger, as regards the problem of representation. It presents initially the Deleuzian argument on what he calls as the dogmatic image of thought. The intention is to highlight the points that, according to the French philosopher, contaminate the philosophy of difference by Heidegger. In a second stage, it addresses the theme of ontological difference on the principle of the German philosopher. Arguments are then reported indicating possible inconsistencies in the criticism of Deleuze, which accuses Heidegger for getting rid of objective assumptions at the expense of giving subjective assumptions.
Jocimara Souza Britto Lob?o,Washington de Jesus Sant’Anna da Franca Rocha,Ardemírio Barros da Silva,Sylvio Carlos Bandeira de Mello e Silva
Revista Sociedade & Natureza , 2005,
Abstract: The environment is always in permanent change keeping its proper dynamics with its own rhythms.However, when the people move themselves occupying specific locations, some transformations can take place, constituting threats for the environment and for the manhimself. These changes are related to the enviroment degradation, which has erosion as one of its most significant processes.To understand this dynamic, it is necessary to model the environment in a way that is possible to identify areas with different degrees of natural vulnerability to erosion and thus provide actions that relieve these impacts.The erosive processes are part of the lithosphere modeling system and have its intensity degree more stable or more intense according to the sum of several physical variables (lithology, leveling, landscape, rainfall and hydrography), biological variables (ecosystem- the type of the original and second growth vegetation) and anthropogenic variables (the type of human occupation and mining activities).The impact of the rain on the soil has its effects reduced because of the vegetation and so the pedogenesis is benefited and the erosive processes minimized. On the other hand, if there is no vegetation or if this is insuficient, morphogenesis becomes more intense and theerosive processes enhanced.
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