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Cationic drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liver. In the proximal tubules, two functionally disparate transport systems are involved which are localized in(More)
Antiplatelet treatment is of fundamental importance in combatting functions/dysfunction of platelets in the pathogenesis of cardiovascular and inflammatory diseases. Dysfunction of anucleate platelets is likely to be completely attributable to alterations in posttranslational modifications and protein expression. We therefore examined the proteome of(More)
Vasodilator-stimulated phosphoprotein (VASP), a substrate of cAMP- and cGMP-dependent protein kinases, is associated with focal adhesions, cell-cell contacts, microfilaments, and highly dynamic membrane regions. VASP, which is expressed in most cell types and in particularly high levels in human platelets, binds to profilin, zyxin, vinculin, F-actin, and(More)
Previous research has suggested that cGMP-dependent protein kinases (cGKs) may play a role in long-term potentiation in hippocampus, but their site of action has been unknown. We examined this question at synapses between pairs of hippocampal neurons in dissociated cell culture. Injection of a specific peptide inhibitor of cGK into the presynaptic but not(More)
Sensors based on fluorescence resonance energy transfer (FRET) are powerful tools to monitor signaling events in living mammalian cells. Here we describe development and use of new sensors for cyclic GMP (cGMP) based on cGMP binding domains from cGMP-dependent protein kinase I (GKI) and from phosphodiesterases (PDEs). The temporal and spatial resolution(More)
OBJECTIVE The natriuretic peptides (NPs), atrial (ANP), B-type (BNP), and C-type (CNP) natriuretic peptides as well as their respective receptor-guanylyl cyclases (GC-A for ANP and BNP, and GC-B for CNP) are expressed in the heart. However, the local role of NPs in the regulation of cardiac contractility and the mutual interactions of NPs remain(More)
Platelets are specialized adhesive cells that play a key role in normal and pathological hemostasis through their ability to rapidly adhere to subendothelial matrix proteins (platelet adhesion) and to other activated platelets (platelet aggregation). NO plays a crucial role in preventing platelet adhesion and aggregation. In platelets, cGMP synthesis is(More)
Many signal transduction pathways are mediated by the second messengers cGMP and cAMP, cGMP- and cAMP-dependent protein kinases (cGK and PKA), phosphodiesterases, and ion channels. To distinguish among the different cGMP effectors, inhibitors of cGK and PKA have been developed including the K-252 compound KT5823 and the isoquinolinesulfonamide H89. KT5823,(More)
OBJECTIVES Platelets, specialized adhesive cells, play key roles in normal and pathological hemostasis through their ability to rapidly adhere to subendothelial matrix proteins (adhesion) and to other activated platelets (aggregation), functions which are inhibited by nitric oxide (NO). Platelets have been reported to be regulated not only by exogenous(More)
LIM and SH3 domain protein (LASP-1) is a specific focal adhesion protein involved in cell migration. Overlay studies demonstrate that LASP-1 directly binds to the proline-rich domains of zyxin, lipoma preferred partner (LPP), and vasodilator-stimulated phosphoprotein (VASP), with zyxin being the most prominent interacting partner. Despite the(More)