spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Raucher, D.
Right arrow Articles by Sheetz, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Raucher, D.
Right arrow Articles by Sheetz, M. P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
Journal of Cell Science 114, 3759-3766 (2001)
© 2001 The Company of Biologists Limited

RESEARCH ARTICLE

Phospholipase C activation by anesthetics decreases membrane-cytoskeleton adhesion

Drazen Raucher1,* and Michael P. Sheetz2

1 Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
2 Department of Biological Sciences, Box 2408, Columbia University, 1212 Amsterdam Ave., New York, NY 10027, USA

*Author for correspondence (e-mail: drazen{at}duke.edu)

Accepted July 3, 2001

Many different amphiphilic compounds cause an increase in the fluid-phase endocytosis rates of cells in parallel with a decrease in membrane-cytoskeleton adhesion. These compounds, however, do not share a common chemical structure, which leaves the mechanism and even site of action unknown. One possible mechanism of action is through an alteration of inositol lipid metabolism by modifying the cytoplasmic surface of the plasma membrane bilayer. By comparing permeable amphiphilic amines used as local anesthetics with their impermeable analogs, we find that access to the cytoplasmic surface is necessary to increase endocytosis rate and decrease membrane-cytoskeleton adhesion. In parallel, we find that the level of phosphatidylinositol 4,5-bisphosphate (PIP2) in the plasma membrane is decreased and cytoplasmic Ca2+ is increased only by permeable amines. The time course of both the decrease in plasma membrane PIP2 and the rise in Ca2+ parallels the decrease in cytoskeleton-membrane adhesion. Inositol labeling shows that phosphatidylinositol-4-phosphate levels are increased by the permeable anesthetics, indicating that lipid turnover is increased. Consistent with previous observations, phospholipase C (PLC) inhibitors block anesthetic effects on the PIP2 and cytoplasmic Ca2+ levels, as well as the drop in adhesion. Therefore, we suggest that PLC activity is increased by amine anesthetics at the cytoplasmic surface of the plasma membrane, which results in a decrease in membrane-cytoskeleton adhesion.

Key words: Local anesthetic, Phospholipase C, Membrane-cytoskeleton adhesion, Calcium release


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




© The Company of Biologists Ltd 2001