JPET Introducing ALZET?ew Model 2006 Pump

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


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 30, 2004; DOI: 10.1124/jpet.104.071068

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.104.071068v1
311/3/1044    most recent
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
Right arrow Author home page(s):
Margaret E. Gnegy
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kantor, L.
Right arrow Articles by Gnegy, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kantor, L.
Right arrow Articles by Gnegy, M. E.


Received for publication May 6, 2004.
Revised August 24, 2004.
Accepted for publication August 30, 2004.

REPEATED AMPHETAMINE COUPLES NOREPINEPHRINE TRANSPORTER AND CALCIUM CHANNEL ACTIVITIES IN PC12 CELLS

Lana Kantor 1, Minjia Zhang 1, Bipasha Guptaroy 2, Yang Hae Park 2, Margaret E. Gnegy 1*

1 Univ. Michigan Med. Sch. 2 Univ. Mich. Med. Sch.

* Address correspondence to: E-mail: pgnegy{at}umich.edu

Abstract

Repeated, intermittent amphetamine enhances efflux of dopamine through the dopamine transporter in rat basal ganglia and through the norepinephrine transporter in rat pheochromocytoma PC12 cells. Extracellular Ca2+ is required for the detection of this enhancement in the rat. In this study we examined the role of Ca2+ and Ca2+ channels in the enhanced amphetamine-induced dopamine efflux that develops in PC12 cells following repeated, intermittent amphetamine. Repeated pretreatment of PC12 cells with 1 µM amphetamine followed by a drug-free period increased amphetamine-induced efflux of dopamine compared to controls. The enhancement in amphetamine-induced dopamine efflux depended upon the presence of extracellular Ca2+ and was inhibited by blockade of N-type and L-type Ca2+ channels. The enhanced dopamine efflux was not altered by tetanus toxin or reserpine, treatments that abrogate synaptic vesicle-mediated, exocytotic dopamine efflux. Measurement of intracellular Ca2+ concentrations using fura-2/AM, revealed that amphetamine increased intracellular Ca2+ by a transporter-dependent mechanism. In amphetamine-pretreated cells, amphetamine elicited a greater increase in intracellular Ca2+; this increase depended upon the presence of extracellular Ca2+ and N-type and L-type Ca2+ channel activity. The enhanced amphetamine-induced dopamine efflux requires Ca2+/calmodulin kinase activity. In vehicle-treated cells, 1 µM amphetamine inhibited the calmodulin kinase activity while it did not in amphetamine-pretreated cells. This study suggests that repeated, intermittent amphetamine couples norepinephrine transporter activity and Ca2+ signaling.


Key words: CaM Kinase II, N-type calcium channel, calcium channel blocker, dopamine release, fura-2, intracellular calcium


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
Y. Wei, J. M. Williams, C. Dipace, U. Sung, J. A. Javitch, A. Galli, and C. Saunders
Dopamine Transporter Activity Mediates Amphetamine-Induced Inhibition of Akt through a Ca2+/Calmodulin-Dependent Kinase II-Dependent Mechanism
Mol. Pharmacol., March 1, 2007; 71(3): 835 - 842.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Dipace, U. Sung, F. Binda, R. D. Blakely, and A. Galli
Amphetamine Induces a Calcium/Calmodulin-Dependent Protein Kinase II-Dependent Reduction in Norepinephrine Transporter Surface Expression Linked to Changes in Syntaxin 1A/Transporter Complexes
Mol. Pharmacol., January 1, 2007; 71(1): 230 - 239.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
R. D. Blakely, L. J. DeFelice, and A. Galli
Biogenic Amine Neurotransmitter Transporters: Just When You Thought You Knew Them
Physiology, August 1, 2005; 20(4): 225 - 231.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. A. Johnson, B. Guptaroy, D. Lund, S. Shamban, and M. E. Gnegy
Regulation of Amphetamine-stimulated Dopamine Efflux by Protein Kinase C {beta}
J. Biol. Chem., March 25, 2005; 280(12): 10914 - 10919.
[Abstract] [Full Text] [PDF]


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

Copyright © 2004 by the American Society for Pharmacology and Experimental Therapeutics.