Caffeine Regulates Neuronal Expression of the Dopamine 2 Receptor Gene
The psychoactive drug caffeine influences neuronal physiology; however, it is unknown whether it can dynamically alter the expression of genes that influence neurotransmission. Here, we report that caffeine stimulates transcription of the dopamine 2 receptor (D2R) gene in PC-12 cells and primary str...
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Published in | Molecular pharmacology Vol. 64; no. 6; pp. 1463 - 1473 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.12.2003
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Subjects | |
Online Access | Get full text |
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Summary: | The psychoactive drug caffeine influences neuronal physiology; however, it is unknown whether it can dynamically alter the
expression of genes that influence neurotransmission. Here, we report that caffeine stimulates transcription of the dopamine
2 receptor (D2R) gene in PC-12 cells and primary striatal cultures and increases D2R protein expression in the striatum. Physiological
doses of caffeine and the specific adenosine 2A receptor antagonist 8-(3-chlorostyryl) caffeine both increased the activity
of a D2R/luciferase reporter construct within 24 h, and simultaneous treatment with 2-[ p -(2-carboxyethyl)phenethylamino]-5â²- N -ethylcarboxamidoadenosine (CGS 21680), a specific adenosine 2A receptor agonist, eliminated this effect. Tests of additional
constructs revealed that specific regions of the D2R promoter (-117/-75) and 5â²-untranslated region (+22/+317) were required
for activation of D2R gene expression by caffeine. In primary striatal cultures, caffeine increased spontaneous firing of
neurons between 12 and 80 min after treatment, whereas it increased D2R mRNA expression after only 4 h. These results indicate
that regulation of D2R gene expression by caffeine occurs after the initial physiological response has subsided. In vivo,
female mice treated with a dose of caffeine (50 mg/kg) showed 1.94- and 2.07-fold increases in D2R mRNA and protein expression,
respectively. In contrast, male mice exhibited a 31% decrease in D2R mRNA expression and showed no changes in D2R protein
expression. Collectively, these results demonstrate for the first time that caffeine alters D2R expression in neurons. They
also suggest that caffeine consumption can lead to sexually dimorphic patterns of gene expression in the brain. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0026-895X 1521-0111 |
DOI: | 10.1124/mol.64.6.1463 |