Identification of novel catecholamine absorbing proteins in the central nervous system

Several pharmacologically active catecholamines have been shown to react covalently with CNS proteins, namely species of 47, 40, 22, and 20 kDa. Of these, the 47-kDa protein showed the greatest incorporation of tritium following treatment with [3H]dopamine, [3H]ADTN, or [3H]N-propyl-norapomorphine. Labeling was accomplished by incubating the tritiated ligands with crude membrane preparations in the absence of reducing agents. These proteins displayed several unique characteristics: 1. The proteins are distributed throughout the CNS, but no evidence was found for their presence in other tissues; 2. The proteins have a unique pharmacological profile, interacting with dopamine, ADTN, N-propyl-norapomorphine, and apomorphine, but not with ligands specific for other proteins known to interact with these compounds; 3. The labeling of these proteins is not inhibited by several similar catecholamines and other catechols, suggesting specific structural requirements; and 4. These proteins exhibited stereoselectivity with respect to this labeling. These results demonstrate the existence of novel CNS proteins capable of covalently absorbing several physiologically important catecholamines in vitro.