Characterization of [ 125 I]ZM241385 binding to adenosine A 2A receptors in thalamus and pineal gland of sheep brain

Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic effects through activation of A 1 , A 2A , A 2B , and A 3 receptor subtypes. In the central nervous system, adenosine has neuromodulatory activity that often manifests as tonic inhibitory control. Adenosine released from the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action that may be mediated by A 2A receptors that are associated with the parafascicular nuclear complex of the posteromedial thalamus. In an effort to define the relative distribution of adenosine A 2A receptors in the sheep diencephalons, we have used a receptor autoradiographic technique utilizing an iodinated radioligand, which has greater sensitivity than the tritiated compound. The distribution of [ 125 I]ZM241385 binding sites in fetal sheep diencephalons indicated that the highest levels of binding were in the parafascicular nuclear complex and the pineal gland. These binding sites were more fully characterized in homogenate radioligand binding assays. These data indicated that [ 125 I]ZM241385 binding sites displayed a pharmacological signature consistent with that of adenosine A 2A receptors and were expressed at similar levels in fetal neonatal, and adult ovine brain. These results have important implications for the functional roles of adenosine in the thalamus and pineal of the sheep brain. Supported by NICHD HD‐18478