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J Appl Physiol (1985). 2009 Feb;106(2):631-9. doi: 10.1152/japplphysiol.90971.2008. Epub 2008 Nov 26.

Mice heterozygous for both A1 and A(2A) adenosine receptor genes show similarities to mice given long-term caffeine.

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1
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. jiangning.yang@ki.se

Abstract

Caffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number of A(1)Rs and A(2A)Rs, achieved by deleting one of the two copies of the A(1)R and A(2A)R genes, would mimic some aspects of long-term caffeine ingestion. The A(1)R and A(2A)R double heterozygous (A(1)R-A(2A)R dHz) mice indeed had approximately one-half the number of A(1)R and A(2A)R, and there were little compensatory changes in A(2B) or A(3) adenosine receptor (A(2B)R or A(3)R) expression. The ability of a stable adenosine analog to activate receptors was shifted to the right by caffeine and in A(1)R-A(2A)R dHz tissue. Caffeine (0.3 g/l in drinking water for 7-10 days) and A(1)R-A(2A)R dHz genotype increased locomotor activity (LA) and decreased heart rate without significantly influencing body temperature. The acute stimulatory effect of a single injection of caffeine was reduced in A(1)R-A(2A)R dHz mice and in mice treated long term with oral caffeine. Thus at least some aspects of long-term caffeine use can be mimicked by genetic manipulation of the A(1)R and A(2A)R.

PMID:
19036889
PMCID:
PMC2644247
DOI:
10.1152/japplphysiol.90971.2008
[Indexed for MEDLINE]
Free PMC Article
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