Abstract
Long-term exposure to cocaine can cause persistent behavioral changes and alterations in neuronal function. One cocaine-regulated mRNA in the rat brain is the beta-1 subunit of the Na+/K+-ATPase pump. We examined both Na+/K+-ATPase function and expression after cocaine treatment of pheochromocytoma cells. One-hour exposure to cocaine did not alter Na+/K+-ATPase activity, as measured by the ouabain-sensitive component of rubidium uptake. Four days of cocaine resulted in an ∼30% decrease in Na+/K+-ATPase activity. Western blot analyses demonstrated an ∼25% decrease in levels of the beta-1 isoform, without changes in pump total alpha subunit levels. Treatment with dopamine type 1 or type 2 receptor agonists for the same period did not affect Na+/K+-ATPase activity. The serotonin-selective reuptake inhibitor paroxetine caused an ∼45% decrease in rubidium uptake after 4 days, whereas pump function was not altered after treatment with either the dopamine-selective reuptake blocker nomifensine or the norepinephrine-selective reuptake blocker desipramine. Chronic treatment with both cocaine and LY 278,584, a serotonin type 3 receptor antagonist, did not replicate the cocaine-associated decrease in pump function. Long-term cocaine exposure regulates expression and function of the Na+/K+-ATPase pump in neuronal-like cells; this regulation is mediated in part via the serotonin type 3 receptor. Similar Na+/K+-ATPase pump regulation in vivo may selectively alter neuronal function in the mammalian brain.
Footnotes
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Send reprint requests to: Scott A. Mackler, Medical Research Service (151C), Philadelphia VAMC, University & Woodland Avenues, Philadelphia, PA 19104.
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↵1 Supported by National Institutes of Health grant DA 00199.
- Abbreviation:
- ECL
- enzymatic chemiluminescence
- 5-HT
- serotonin
- NGF
- nerve growth factor
- PC
- pheochromocytoma
- Rb+
- rubidium
- HEPES
- N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid
- Received November 12, 1997.
- Accepted January 23, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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