IDENTIFICATION OF NOVEL CATECHOLAMINE ABSORBING PROTEINS IN THE CENTRAL-NERVOUS-SYSTEM

Several pharmacologically active catecholamines have been shown to rea ct 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 [H-3]dopamine, [H-3]ADTN, or [H-3]N- propyl-norapomorphine. Labeling was accomplished by incubating the tri tiated ligands with crude membrane preparations in the absence of redu cing agents. These proteins displayed several unique characteristics: 1. The proteins are distributed throughout the CNS, but no evidence wa s found for their presence in other tissues; 2. The proteins have a un ique pharmacological profile, interacting with dopamine, ADTN, N-propy l-norapomorphine, and apomorphine, but not with ligands specific for o ther proteins known to interact with these compounds; 3. The labeling of these proteins is not inhibited by several similar catecholamines a nd other catechols, suggesting specific structural requirements; and 4 . These proteins exhibited stereoselectivity with respect to this labe ling. These results demonstrate the existence of novel CNS proteins ca pable of covalently absorbing several physiologically important catech olamines in vitro.