Age-related changes in cardiac adenosine receptor expression.

Adenosine is an important cardioprotective agent that works via several adenosine receptor (ADOR) subtypes to regulate cardiovascular activity. It is well established that functional responses to adenosine decline with age. What is unclear, though, is whether these changes occur at the receptor, second messenger or translational level. In this study we determined the effect of age on cardiac adenosine receptor expression using the housekeeping gene 18S rRNA versus the adenosine A(2B) receptor gene as internal controls. Absolute quantification showed that no age-related changes occurred in the expression of 18S rRNA or adenosine A(2B) receptor internal control genes. Subsequently, relative analysis of the adenosine receptor subtypes using 18S rRNA found a significant age-related reduction in the expression of the adenosine A(1) receptor (5.5-fold), with no changes in the expression of the adenosine A(2A), A(2B) and A(3) receptors. When using the expression of the adenosine A(2B) receptor as the internal control gene, a significant down regulation of both the adenosine A(1) (5.4-fold) and A(2A) (2.2-fold) receptors with no change in the expression of adenosine A(3) receptor was found. Therefore, the high level of expression of the 18S rRNA housekeeping gene was found to mask a significant change in expression of the adenosine A(2A) receptor with age. Ultimately, these findings show an age-related reduction in adenosine A(1) and A(2A) receptor expression in rat heart.