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Transduction Signal (transduction + signal)
Selected AbstractsMechanisms of renal hyporesponsiveness to ANP in heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2003A. Charloux Abstract The atrial natriuretic peptide (ANP) plays an important role in chronic heart failure (CHF), delaying the progression of the disease. However, despite high ANP levels, natriuresis falls when CHF progresses from a compensated to a decompensated state, suggesting emergence of renal resistance to ANP. Several mechanisms have been proposed to explain renal hyporesponsiveness, including decreased renal ANP availability, down-regulation of natriuretic peptide receptors and altered ANP intracellular transduction signal. It has been demonstrated that the activity of neutral endopeptidase (NEP) is increased in CHF, and that its inhibition enhances renal cGMP production and renal sodium excretion. In vitro as well as in vivo studies have provided strong evidence of an increased degradation of intracellular cGMP by phosphodiesterase in CHF. In experimental models, ANP-dependent natriuresis is improved by phosphodiesterase inhibitors, which may arise as new therapeutic agents in CHF. Sodium-retaining systems likely contribute to renal hyporesponsiveness to ANP through different mechanisms. Among these systems, the renin-angiotensin-aldosterone system has received particular attention, as angiotensin II and ANP have renal actions at the same sites and inhibition of angiotensin-converting enzyme and angiotensin-receptor blockade improve ANP hyporesponsiveness. Less is known about the interactions between the sympathetic nervous system, endothelin or vasopressin and ANP, which may also blunt ANP-induced natriuresis. To summarize, renal hyporesponsiveness to ANP is probably multifactorial. New treatments designed to restore renal ANP efficiency should limit sodium retention in CHF patients and thus delay the progression to overt heart failure. [source] Synthesis and Anion-Binding Properties of Novel Redox-Active Calixarene ReceptorsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 25 2008Estelle Métay Abstract A novel synthetic approach towards redox-active calixarene-based receptors is described in which ferrocene fragments were introduced at the lower rim through anion-binding urea or amide connections. These derivatives were prepared in one pot by treating an amine-containing calixarene with ferrocenecarboxylic acid in the presence of diphenylphosphoryl azide and diisopropylethylamine. This method allows a convergent approach to these receptors and is readily adaptable to the introduction of other urea substituents. The anion-binding properties of these artificial receptors have been revealed by NMR spectroscopy and thoroughly investigated by electrochemical methods. We have assessed the importance of the urea,phosphate bonds in the observed electrochemical response by studying receptors in which the ferrocene reporters and binding fragments are closely associated or fully disconnected through a long alkyl chain. The experimental results clearly show the utmost importance of ion-pairing effects in the electrochemical recognition process, which account for most of the transduction signal in organic apolar media. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] A Cascade FRET-Mediated Ratiometric Sensor for Cu2+Ions Based on Dual Fluorescent Ligand-Coated Polymer NanoparticlesCHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2009Michel Frigoli Dr. Abstract Core-shell type dual fluorescent nanoparticles (NPs) in the 16,nm diameter range with a selective ligand (cyclam) attached to the surface and two fluorophores,9,10-diphenyl-anthracene (donor, D) and pyrromethene PM,567 (acceptor, A),embedded within the polymer core were synthesized and their fluorescent and copper-sensing properties were studied and compared to single D -doped and A -doped NPs. The acceptor (A) and donor (D) dyes were chosen to allow two sequential Förster resonance energy transfer (FRET) processes from D to A and from the encapsulated dyes to copper complexes that form at the surface and act as quenchers. NPs with different D/A loads were readily obtained by two consecutive entrapments of the dyes. Dual NPs present tunable fluorescence emission that is dependent on the doping ratio. FRET from D to A results in sensitized emission from A upon excitation of D, with FRET efficiencies reaching 80,% at high acceptor loads. A 9-fold amplification of the signal of A is observed at high D -to- A ratios. Single- and dual-dye-doped NPs were used to detect the presence of cupric ions in water by using the quenching of fluorescence as a transduction signal. In accordance with the spectral overlaps and the values of the critical distance (R0) of D, and A,copper complex pairs, the acceptor is much more sensitive than the donor. In dual fluorescent NPs, the sensitized emission of A is efficiently attenuated whereas the remaining emission of D is much less affected, allowing the detection of copper in a ratiometric manner upon excitation at a single (D) wavelength. Dual-dye-doped NPs with the highest acceptor loads (23,A -per-NP) were found to be the most sensitive for the detection of copper over a wide range of concentrations (20,nM to 8.5,,M). Owing to its great convenience and modularity, the cascade FRET strategy based on dual fluorescent NPs holds great promise for the design of various sensing nanodevices. [source] The Ghrelin/Obestatin Balance in the Physiological and Pathological Control of Growth Hormone Secretion, Body Composition and Food IntakeJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010R. Hassouna Ghrelin and obestatin are two gastrointestinal peptides obtained by post-translational processing of a common precursor, preproghrelin. Ghrelin is an orexigenic and adipogenic peptide and a potent growth hormone secretagogue (GHS) modified by the enzyme ghrelin- O -acyl-transferase to bind and activate its receptor, the GHS-R. The ghrelin/GHS-R pathway is complex and the effects of ghrelin on GH secretion, adiposity and food intake appear to be relayed by distinct mechanisms involving different transduction signals and constitutive activity for the GH-R, different cofactors as modulators of endogenous ghrelin signalling and/or alternative ghrelin receptors. The discovery of obestatin in 2005 brought an additional level of complexity to this fascinating system. Obestatin was initially identified as an anorexigenic peptide and as the cognate ligand for GPR39, but its effect on food intake and its ability to activate GPR39 are still controversial. Although several teams failed to reproduce the anorexigenic actions of obestatin, this peptide has been shown to antagonise GH secretion and food intake induced by ghrelin and could be an interesting pharmacological tool to counteract the actions of ghrelin. Ghrelin and obestatin immunoreactivities are recovered in the blood with an ultradian pulsatility and their concentrations in plasma vary with the nutritional status of the body. It is still a matter of debate whether both hormones are regulated by independent mechanisms and whether obestatin is a physiologically relevant peptide. Nevertheless, a significant number of studies show that the ghrelin/obestatin ratio is modified in anorexia nervosa and obesity. This suggests that the ghrelin/obestatin balance could be essential to adapt the body's response to nutritional challenges. Although measuring ghrelin and obestatin in plasma is challenging because many forms of the peptides circulate, more sensitive and selective assays to detect the different preproghrelin-derived peptides are being developed and may be the key to obtaining a better understanding of their roles in different physiological and pathological conditions. [source] | |||||||||||||