Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic actions through activation of A1, A2A, A2B and A3 adenosine receptor subtypes. In the central nervous system, adenosine's action in neurons is manifested in its modulation of tonic inhibitory control. Adenosine released in the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action suggested to be mediated by A2A receptors in the posteromedial thalamus. In an effort to more accurately define the spatial distribution of adenosine A2A receptors in fetal sheep diencephalon, we have used a receptor autoradiographic technique utilizing an iodinated radioligand [125I]ZM 241385, which has greater sensitivity and resolution than the tritiated compound. The distribution of ligand binding sites in the fetal sheep diencephalon indicated that the highest levels of binding were in select thalamic nuclei, including those implicated in hypoxic depression of fetal breathing, and the pineal. Given the high density of labeled A2A receptors in the pineal, these sites were characterized more fully in homogenate radioligand binding assays. These data indicate that [125I]ZM 241385 binding sites display a pharmacological signature consistent with that of adenosine A2A receptors and are expressed at similar levels in fetal, lamb and adult ovine brain. The adenosine A2A receptor pharmacologic signature of the [125I]ZM 241385 binding site in pineal cell membranes generalized to the site characterized in membranes derived from other portions of the lamb thalamus, including the sector involved in hypoxic inhibition of fetal breathing. These results have important implications for the functional roles of adenosine A2A receptors in the thalamus and pineal of sheep brain.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology