utrn(-/-) ;mdx mice are therefore a very useful model for investigating potential cardiac therapies. (C) 2012 Elsevier B.V. All rights reserved.”
“P>We investigated the regulatory pathways responsible for agonist-induced internalization and down-regulation of G(q) protein-coupled histamine H-1-receptors in Chinese hamster ovary cells. Histamine-induced internalization and down-regulation of H-1-receptors were detected Temsirolimus as the loss of [3H]mepyramine binding sites on intact cells accessible to hydrophilic and hydrophobic H-1-receptor antagonists,

pirdonium and mepyramine, respectively. Pretreatment of cells with 0.1 mM histamine for 30 min at 37 degrees C induced internalization as well as down-regulation of H-1-receptors, both of which were inhibited either in the presence of an inhibitor against G protein-coupled receptor kinases (ZnCl2) or under hypertonic conditions where clathrin-dependent endocytosis is known to be inhibited, but were not affected by inhibitors against caveolae/raft-dependent endocytosis (filipin and nystatin). Down-regulation of H-1-receptors, but not their internalization, was inhibited by protein kinase C inhibitors (chelerythrin or GF109203X), a ubiquitin E1 inhibitor (UBEI-41) and proteasome inhibitors (lactacystin and MG-132). Anlotinib Neither a Ca2 + /calmodulin-dependent protein kinase II inhibitor (KN-62) nor lysosomal protease

inhibitors (E-64, leupeptin, chloroquine and NH4Cl) affected the internalization and down-regulation of H-1-receptors. These results suggest that H-1-receptors internalize upon agonist

stimulation via G protein-coupled receptor kinase/clathrin-dependent but caveolae/raft-independent mechanisms and are delivered to proteasomes, preferentially to lysosomes, for their prompt down-regulation.”
“Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals.\n\nThe aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance.\n\nNon-sleep deprived healthy volunteers (n = 24) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated Selleckchem Sapanisertib coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance.\n\nThe results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p = 0.024) and second hour (p = 0.019) after the break. Similarly, the standard deviation of speed (p = 0.024; p = 0.