Novel antagonists of alcohol inhibition of l1-mediated cell adhesion: multiple mechanisms of action.

@article{Wilkemeyer2002NovelAO,
  title={Novel antagonists of alcohol inhibition of l1-mediated cell adhesion: multiple mechanisms of action.},
  author={Michael F. Wilkemeyer and Carrie E Menkari and Michael E. Charness},
  journal={Molecular pharmacology},
  year={2002},
  volume={62 5},
  pages={
          1053-60
        }
}
1-Octanol antagonizes ethanol inhibition of L1-mediated cell adhesion and prevents ethanol teratogenesis in mouse whole embryo culture. Herein, we identify a new series of alcohol antagonists and study their mechanism of action. Cell aggregation assays were carried out in ethanol-sensitive, human L1-transfected NIH/3T3 cells in the absence and presence of 100 mM ethanol or 2 mM 1-butanol and candidate antagonists. Antagonist potency for 1-alcohols increased progressively over 5 log orders from… Expand
Peptide Antagonists of Ethanol Inhibition of L1-Mediated Cell-Cell Adhesion
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Two structurally unrelated classes of compounds, alcohols and small polypeptides, share two common actions: antagonism of ethanol inhibition of L1-mediated cell adhesion and prevention of ethanol teratogenesis. Expand
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The findings suggest that D-NAP and 1-octanol selectively interact with NMDA receptors in an ethanol-dependent manner, further implicating the L1 cell adhesion molecule in alcohol-related brain disorders. Expand
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Two Alcohol Binding Residues Interact across a Domain Interface of the L1 Neural Cell Adhesion Molecule and Regulate Cell Adhesion*
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These findings support the hypothesis that alcohol binding within a pocket bordered by Glu-33 and Tyr-418 inhibits L1 adhesion by disrupting the Ig1-Ig4 interaction. Expand
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TLDR
The data show that TGF beta1 alters cell migration in the developing cortex and that the TGFbeta1 system is a target of ethanol toxicity. Expand
Linking acquired neurodevelopmental disorders to defects in cell adhesion
  • D. Greenberg
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
Findings are reported that link cell adhesion molecules (CAMs) to an important, preventable mental retardation syndrome and activate transduction pathways that involve inositol phosphates, mobilization of intracellular calcium, voltage-gated calcium influx, and cAMP. Expand
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References

SHOWING 1-10 OF 44 REFERENCES
Antagonists of alcohol inhibition of cell adhesion.
TLDR
Notably strict structural requirements for alcohol inhibition of cell-cell adhesion are demonstrated in L1-transfected NIH 3T3 fibroblasts and in NG108-15 neuroblastoma x glioma hybrid cells treated with BMP-7, an inducer of L1 and neural cell adhesion molecule. Expand
Alcohol inhibits cell-cell adhesion mediated by human L1 [published erratum appears in J Cell Biol 1996 Jun;133(5):1139-40]
TLDR
Because L1 plays a role in both neural development and learning, ethanol inhibition of L1-mediated cell-cell interactions could contribute to FAS and ethanol-associated memory disorders. Expand
Ethanol inhibits the function of 5-hydroxytryptamine type 1c and muscarinic M1 G protein-linked receptors in Xenopus oocytes expressing brain mRNA: role of protein kinase C.
TLDR
The results indicate that certain types of receptor-G protein interactions are more susceptible than others to uncoupling by ethanol and that ethanol inhibition of 5-HT1c receptors requires PKC-mediated phosphorylation. Expand
Ethanol inhibits neural cell-cell adhesion.
TLDR
It is shown that concentrations of ethanol achieved during social drinking inhibit hOP-1-induced cell clustering without affecting cell proliferation, the induction and cell surface expression of N-CAM and L1, or the alternative splicing and sialylation of N -CAM. Expand
Enhancement of glycine receptor function by ethanol: role of phosphorylation
TLDR
Results indicate that phosphorylation by PKC of the homomeric α1 glycine receptors subunit modulates ethanol potentiation, but not the function of the glycine receptor. Expand
Characterization of Ethanol‐Sensitive and Insensitive Fibroblast Cell Lines Expressing Human L1
TLDR
It is shown that ethanol inhibits L1‐mediated cell‐cell adhesion in fibroblast cell lines stably transfected with human L1, suggesting that L1 may exist in an alcohol‐sensitive or an alcohol-insensitive state that may be governed by host cell factors. Expand
Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes.
TLDR
Ethanol and volatile anesthetics inhibit mGluR5 because they promote PKC-mediated phosphorylation, and mutation of a PKC consensus site of mGLUR5 abolished the inhibitory effects of halothane, F3, and ethanol. Expand
Ethanol Inhibits L1-mediated Neurite Outgrowth in Postnatal Rat Cerebellar Granule Cells*
TLDR
One mechanism of ethanol’s toxicity to the developing central nervous system may be the inhibition of L1-mediated neurite outgrowth, which is similar to those of patients with mutations in L1, a neural cell adhesion molecule. Expand
Alcohol inhibition of cell adhesion in BMP-treated NG108-15 cells.
TLDR
These data suggest that ethanol inhibits cell-cell adhesion in OP-1-treated NG108-15 cells by interacting directly or indirectly with the neuronal isoform of L1. Expand
Activation of cyclic AMP-dependent protein kinase reverses tolerance of a nucleoside transporter to ethanol.
TLDR
The results suggest that ethanol sensitivity of adenosine transport is regulated by PKA and protein phosphatase activities in NG108-15 cells, and that the effects of chronic ethanol exposure on adenoine transport can be reversed by activating PKA. Expand
...
1
2
3
4
5
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