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Pharmacological Drugs (pharmacological + drug)
Selected AbstractsMapacalcine specifically blocks hypoxia-induced calcium influx in rat hepatocytesFEBS JOURNAL, Issue 9 2003Dominique Crenesse Post ischaemic cell calcium invasion has been described as one of the main causes of graft failure. Protective effects of calcium antagonists have been investigated but are not convincing and their mechanisms of action remain unclear. In this work we tested the protective effect of a new calcium inhibitor described to block a calcium current insensitive to all known calcium blockers. Specific mapacalcine receptors were first characterized on rat hepatocytes membranes using the 125I-labeled mapacalcine. 45Ca fluxes were then measured on cultured hepatocytes submitted (or not) to an hypoxic period. The action of mapacalcine was investigated on the ischaemia-induced calcium influx. We demonstrate here that: (a) there are specific receptors for mapacalcine in rat hepatocytes; (b) Mapacalcine is able to specifically block ischaemia,induced calcium influx with an IC50 of 0.3 µm and does not significantly interact with the basal calcium flux. Our work demonstrates that the mapacalcine receptor is a cellular structure directly involved in the phenomenon of postischaemic cell invasion by calcium. Specific block of ischaemia-induced Ca2+ influx by mapacalcine suggests that the development of a panel of pharmacological drugs acting on this receptor could lead to the discovery of therapeutic agents able to protect cells against one of the events responsible for organ failure after transplantation or simply after an ischaemic period. Moreover, identification of the cellular protein which binds mapacalcine may become an important step in the research of mechanisms involved in postischaemic cell invasion by calcium. [source] Continuum and discrete calculation of fractional contributions to solvation free energyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2003Antonio Morreale Abstract Approaches to compute fractional contributions to the solvation free energy are developed in the context of continuum self consistent reaction field calculations (both classical and quantum mechanical), as well as in the framework of discrete molecular dynamics simulations. It is found that for a series of typical pharmacological drugs there is a good agreement between the different fractional descriptions. Algorithms reported here can be easily applied as molecular descriptors in the context of quantitative structure-activity relationships. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1610,1623, 2003 [source] Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2003Yasuhisa Kurogi Abstract Mesangial cells (MC) serve a number of functions in the renal glomerular capillary including structural support of the capillary tuft, modulation of glomerular hemodynamics, and a phagocytic function allowing removal of macromolecules and immune complexes. The proliferation of MC is a prominent feature of glomerular disease including IgA nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and diabetic nephropathy. In experimental animal models of nephritis, MC proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium and glomerulosclerosis. Reduction of MC proliferation in glomerular disease models by treatment with heparin, low-protein diet, or antibodies to platelet-derived growth factor (PDGF), have been shown to reduce extracellular matrix expansion and glomerulosclerotic changes. Therefore, MC proliferation inhibitors may offer therapeutic opportunities for the treatment of proliferative glomerular disease. It is also known that the MC proliferation is inhibited by many kinds of pharmacological drugs, for example, angiotensin converting enzyme (ACE) inhibitors, leukotriene D4 (LTD4) antagonists, PDGF inhibitors, matrix metalloproteinases (MMP) inhibitors, 3-hydroxy-3 methyl glutaryl-coenzymeA (HMG-CoA) inhibitors, cyclin-dependent kinases (CDK) inhibitors, and others. This review summarizes the recently reported MC proliferation inhibitors with their pharmacological properties on the basis of their chemical structures. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 15,31, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10028 [source] Isolated plant nuclei as mechanical and thermal sensors involved in calcium signallingTHE PLANT JOURNAL, Issue 1 2004Tou Cheu Xiong Summary Calcium signals in the nucleus elicit downstream effects that are distinct from those of cytosolic calcium signals. In the present work, we have evaluated the ability of plant nuclei to sense stimuli directly and to convert them into calcium changes. We show that individual mechanical stimulation of isolated nuclei elicits a single calcium transient at acidic pHs, whereas a series of stimulations leads to oscillations whose frequency reflects that of the stimuli. Conversely, at alkaline pHs, nuclei respond to temperature but not to stretch. The stretch- and the temperature-activated processes differ by their sensitivity to pharmacological drugs known to affect ion channel activities in animal cells. Our data demonstrate that isolated nuclei are able to gauge physical parameters of their environment. This might have a profound influence on the functioning of calcium-dependent processes known to control a large array of molecular events in the nucleus. [source] | ||||||||||