The ontogeny of cardiac and neural A1 adenosine receptor expression in rats

To provide insights into the sites and mechanisms of adenosine action during fetal life, the ontogeny of A1 adenosine receptor (A1AR) expression was studied in rats. Using in situ hybridization and receptor binding assays, A1AR expression was examined at gestational days (GD) 8, 11, 14, 17, and 21. At GD 8, A1AR mRNA expression was detected in the myocardium but not in other fetal structures. At GD 11, A1AR mRNA was present in the atria, but not in the ventricles or neural structures. At GD 14, A1AR mRNA was present in the atria and the pontine neuroectoderm, the thalamus, and the ventral horn of the spinal cord. At GD 14, A1ARs were first detectable using [3H]DPCPX (8-cyclopentyl-1,3-dipropylxanthine). Functional binding sites were highest in the atria and present at low levels in brain. When GD 17 was reached, patterns of A1AR expression in the brain were similar to those observed in adult animals. Sites of heavy labeling included the spinal cord, medulla, pons, midbrain, thalamus, and the hippocampus. When pre- and postnatal tissue concentrations of A1ARs were compared, cardiac A1AR receptor concentrations were similar. However, postnatal brain A1AR levels were considerably greater than in fetuses. These data identify the atria as a prominent site of fetal A1AR expression and show that the A1AR gene is one of the earliest expressed G protein-coupled receptor genes in the heart. A1AR expression in brain lags behind cardiac expression in early stages of gestation and exceeds cardiac A1AR expression with progressive maturation. A1ARs may therefore influence the heart and brain during critical periods of fetal development.