CHANGES IN MYOCARDIAL A(1) ADENOSINE RECEPTOR AND MESSAGE LEVELS DURING FETAL DEVELOPMENT AND POSTNATAL MATURATION

Previously we have shown myocardial adenosine A(1) receptors are up-re gulated during the newborn period. The timing of the increase or the m echanism of the changes are not known. The purpose of the present stud y was to (1) determine the time course of increased A(1) adenosine rec eptors during fetal development and (2) determine if A(1) adenosine re ceptor regulation is secondary to changes in A(1) receptor mRNA levels . A(1) adenosine receptor density was determined in whole hearts from fetal rats at 14 and 19 days' gestation and from newborn and adult rat s using standard receptor-binding techniques. A quantitative PCR assay was developed to measure A(1) adenosine receptor mRNA using total RNA samples from the above ages. A(1) receptor density (fmol receptor/mg protein) increased during late gestation (79 +/- 14 and 122 +/- 7 in 1 4 and 19 days' gestation respectively) peaked during the newborn perio d (136 +/- 12) and decreased in the adult rat (36 +/- 5). A(1) recepto r message levels (fg message/mu g total RNA) changed in parallel to re ceptor 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 A(1) receptor density and the increased receptor density in the newborn heart suppo rts a possible role for the A(1) receptor in the transition to the ext rauterine circulation.