The acute effects of ethanol on dopamine (DA) release and clearance in the caudate-putamen were evaluated in wild-type and dopamine transporter (DAT) knockout (DAT-KO) mice, using microdialysis and voltammetry. Dialysate DA levels were elevated, approximately 80% above baseline levels, after administration of 2 g/kg ethanol in both wild-type and DAT-KO mice. In brain slices containing the caudate-putamen, a low (20 mM) concentration of ethanol produced no change in electrically stimulated DA release in either wild-type or DAT-KO mice. A high concentration (200 mM) of ethanol caused a similar decrease in DA release in slices from both types of mice. DA clearance was unaltered across the genotypes at low and high concentrations of ethanol. The fact that ethanol had similar effects in wild-type and DAT-KO mice, measured by in vivo microdialysis or brain slice voltammetry, supports the idea that acute ethanol does not interact with the DAT to produce its effects on the DA system.
Conjugation of antibiotics with benzoxaborole derivatives provides antibiotics with new and useful properties. Teicoplanin aglycone-benzoxaborole derivatives overcome resistance of Gram-positive bacteria to vancomycin.
Ten
protein kinase C (PKC) isozymes play divergent roles in signal transduction.
Because of sequence similarities, it is particularly difficult to
generate isozyme-selective small molecule inhibitors. In order to
identify such a selective binder, we derived a pharmacophore model
from the peptide EAVSLKPT, a fragment of PKCε that inhibits
the interaction of PKCε and receptor for activated C-kinase
2 (RACK2). A database of 330 000 molecules was screened in
silico, leading to the discovery of a series of thienoquinolines that
disrupt the interaction of PKCε with RACK2 in vitro. The most
active molecule, N-(3-acetylphenyl)-9-amino-2,3-dihydro-1,4-dioxino[2,3-g]thieno[2,3-b]quinoline-8-carboxamide
(8), inhibited this interaction with a measured IC50 of 5.9 μM and the phosphorylation of downstream target
Elk-1 in HeLa cells with an IC50 of 11.2 μM. Compound 8 interfered with MARCKS phosphorylation and TPA-induced translocation
of PKCε (but not that of PKCδ) from the cytosol to the
membrane. The compound reduced the migration of HeLa cells into a
gap, reduced invasion through a reconstituted basement membrane matrix,
and inhibited angiogenesis in a chicken egg assay.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.