Interplay among catecholamine systems: Dopamine binds to α ₂-adrenergic receptors in birds and mammals

Dopaminergic and adrenergic receptors are G-protein-coupled receptors considered to be different based on their pharmacology and signaling pathways. Some receptor subtypes that are members of one family are actually closer in phylogenetic terms to some subtypes belonging to the other family, suggesting that the pharmacological specificity among these receptors from different families is not perfect. Indeed, evidence is accumulating that one amine can cross-talk with receptors belonging to the other system. However, most of these observations were collected in vitro using artificial cell models transfected with cloned receptors, so that the occurrence of this phenomenon in vivo as well as its distribution in the central nervous system is not known. In this study the pharmacological basis of possible in vivo interactions between dopamine and α₂-adrenergic receptors was investigated in quail, zebra finches, and rats. Binding competitions showed that dopamine displaces the binding of the selective α ₂-adrenergic ligand, [³H]RX821002, in the brain of the three species with an affinity ≈10-28-fold lower than that of norepinephrine. Dopamine also displaces with an affinity 3-fold lower than norepinephrine the binding of [³H]RX821002 to human α_h2A-adrenergic receptors expressed in Sf9 cells. The anatomical distribution of this interaction was assessed in brain slices of quail and rat based on autoradiographic methods. Both norepinephrine and dopamine significantly displace [³H]RX821002 binding in all brain nuclei considered. Together, these data provide evidence for an interaction between the dopaminergic and noradrenergic systems in the vertebrate brain, albeit with species variations.