Am J Physiol Cell Physiol Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 265: C422-C431, 1993;
0363-6143/93 $5.00
This Article
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ecay, T. W.
Right arrow Articles by Valentich, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ecay, T. W.
Right arrow Articles by Valentich, J. D.

AJP - Cell Physiology, Vol 265, Issue 2 C422-C431, Copyright © 1993 by American Physiological Society

ARTICLES

Lovastatin inhibits cAMP- and calcium-stimulated chloride secretion by T84 cells

T. W. Ecay and J. D. Valentich
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.

Isoprenylated proteins function in the processes of signal transduction and membrane vesicle trafficking. To investigate the role of isoprenylated proteins in secretagogue-stimulated epithelial ion transport, we studied the effects of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca(2+)-stimulated Cl- secretion by monolayers of T84 colonic epithelial cells. Lovastatin reduces protein isoprenylation in many cell types. In T84 cells, lovastatin reversibly inhibits forskolin-stimulated equivalent short-circuit current (I(sc)eq) by 50% after 2 days of treatment. The concentration of lovastatin resulting in half-maximal effects on forskolin-stimulated I(sc)eq is consistent with inhibition of protein isoprenylation, and lovastatin effects on forskolin-stimulated I(sc)eq are not associated with inhibition of cholesterol or glycoprotein biosynthesis. Lovastatin blocks N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate- and ionomycin-stimulated Isc, suggesting that it inhibits a process beyond the stimulation of cAMP and Ca2+ second-messenger systems. In monolayers in which the basolateral membrane has been permeabilized with nystatin, lovastatin inhibits cAMP activation of a diphenylamine-2-carboxylate-sensitive, apical membrane Cl- conductance. Our results are consistent with the hypothesis that an isoprenylated protein is involved in the regulation of a secretagogue-activated apical membrane Cl- conductance in T84 cells.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
J. L. Dickson, T. D. Conner, and T. W. Ecay
Inhibition of phosphatidylinositol 3-kinase does not alter forskolin-stimulated Cl- secretion by T84 cells
Am J Physiol Cell Physiol, May 1, 2000; 278(5): C865 - C872.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online