Changes in myocardial A1 adenosine receptor and message levels during fetal development and postnatal maturation

Previously we have shown myocardial adenosine A1 receptors are up-regulated during the newborn period. The timing of the increase or the mechanism of the changes are not known. The purpose of the present study was to (1) determine the time course of increased A1 adenosine receptors during fetal development and (2) determine if A1 adenosine receptor regulation is secondary to changes in A1 receptor mRNA levels. A1 adenosine receptor density was determined in whole hearts from fetal rats at 14 and 19 days' gestation and from newborn and adult rats using standard receptor-binding techniques. A quantitative PCR assay was developed to measure A1 adenosine receptor mRNA using total RNA samples from the above ages. A1 receptor density (fmol receptor/mg protein) increased during late gestation (79 +/- 14 and 122 +/- 7 in 14 and 19 days' gestation respectively) peaked during the newborn period (136 +/- 12) and decreased in the adult rat (36 +/- 5). A1 receptor message levels (fg message/microgram total RNA) changed in parallel to receptor density (7.2 +/ 1.7, 15.6 +/- 1.8, 19.9 +/- 4.3 and 9.9 +/- 1.3 in 14 and 19 days' gestation, newborn and adult respectively). These results provide evidence for transcriptional control of A1 receptor density and the increased receptor density in the newborn heart supports a possible role for the A1 receptor in the transition to the extrauterine circulation.