JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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 Leslie, S. W.
Right arrow Articles by Farrar, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leslie, S. W.
Right arrow Articles by Farrar, R. P.

Inhibition of fast- and slow-phase depolarization-dependent synaptosomal calcium uptake by ethanol

SW Leslie, E Barr, J Chandler and RP Farrar

Uptake of 45Ca++ by synaptosomes isolated from cerebral cortex, cerebellum, midbrain and brain stem of male, Sprague-Dawley rats was measured at 1-, 3-, 5-, 15-, 30- and 60-sec time periods. At 1 sec, the Ca++ uptake rate by cerebrocortical synaptosomes was 1.45 mumol/sec/g of protein, whereas the 60-sec rate was 0.03 mumol/sec/g of protein. In vitro addition of ethanol, 80 mM, inhibited depolarization-dependent (65 mM KCl) 45Ca++ uptake by synaptosomes but the time-response relationships varied depending upon the brain region studied. In cerebrocortical synaptosomes, ethanol significantly inhibited only the fast-phase component of 45Ca++ uptake (1 and 3 sec). Ethanol inhibited 45Ca++ uptake by midbrain synaptosomes at all measurement times studied (1, 3, 5 and 15 sec), whereas in cerebellum and brain stem ethanol inhibited 45Ca++ uptake at 3- and 5-sec time periods. Ethanol at concentrations of 25, 50, 100 and 150 mM inhibited 45Ca++ uptake by 9.0, 15.9, 24.8 and 30.7%, respectively, in cerebrocortical synaptosomes. In vitro ethanol, 80 mM, added to cerebrocortical synaptosomes isolated from rats fed a nutritionally adequate liquid ethanol diet did not significantly inhibit depolarization-dependent 45Ca++ uptake. The results of this study show that pharmacologically relevant ethanol concentrations inhibit voltage-dependent 45Ca++ uptake into synaptosomes. This inhibitory action may, at least in part, underlie some of the intoxicating effects of ethanol. In addition, chronic administration of ethanol resulted in an apparent adaptive response such that addition of ethanol no longer blocked 45Ca++ uptake. This adaptive response involving the calcium channel may represent a cellular mechanism for functional tolerance development.

Volume 225, Issue 3, pp. 571-575, 06/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
J. Neurophysiol.Home page
A. W. Hendricson, J. R. Sibbald, and R. A. Morrisett
Ethanol Alters the Frequency, Amplitude, and Decay Kinetics of Sr2+-Supported, Asynchronous NMDAR mEPSCs in Rat Hippocampal Slices
J Neurophysiol, June 1, 2004; 91(6): 2568 - 2577.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
A. W. Hendricson, M. P. Thomas, M. J. Lippmann, and R. A. Morrisett
Suppression of L-Type Voltage-Gated Calcium Channel-Dependent Synaptic Plasticity by Ethanol: Analysis of Miniature Synaptic Currents and Dendritic Calcium Transients
J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 550 - 558.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. H. Gerstin Jr., T. McMahon, J. Dadgar, and R. O. Messing
Protein Kinase Cdelta Mediates Ethanol-induced Up-regulation of L-type Calcium Channels
J. Biol. Chem., June 26, 1998; 273(26): 16409 - 16414.
[Abstract] [Full Text] [PDF]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
 Molecular Interventions Drug Metabolism and Disposition

Copyright © 1983 by the American Society for Pharmacology and Experimental Therapeutics.