Influences of adenosine on the fetus and newborn

Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. In contrast to most neurotransmitters, adenosine is released by all cells and is present in all tissues. The adenosinergic system is therefore not dependent on the presence of mature synaptic structures or an intact autonomic nervous system for its release. However, similar to other signaling molecules, adenosine levels are dynamically regulated and increase with increased tissue activity, hypoxia, or stress. Local adenosine concentrations thus provide a "humoral barometer" of acute changes in cellular physiology. The receptors that transduce adenosine action include A1, A2a, A2b, and A3 adenosine receptors. These receptors differ in their affinities for adenosine and in patterns of tissues expression. During development A1 adenosine receptors (A1ARs) are especially important, and A1ARs are among the earliest receptors expressed in the embryonic brain and heart. In the developing heart, the adenosinergic system is the dominant regulator of fetal cardiac function and A1AR activation inhibits cardiac cell division leading to cardiac hypoplasia. In the forming central nervous system, A1AR activation potently inhibits the development of axons and can lead to leukomalacia. These recent data suggest that adenosine is an important modulator of mammalian development.