Catecholamines bind to enkephalins, morphiceptin, and morphine

Nuclear magnetic resonance spectroscopy, pH titration, and color reactions demonstrate that the catecholamines dopamine, epinephrine, and norepinephrine bind to the enkephalins. Binding constants are c. 6 X 10(3) per mole. Catecholamines also bound to the mu opiate receptor agonist morphiceptin (Tyr-Pro-Phe-Pro-NH2). Very little binding was found to enkephalin and morphiceptin fragments and analogues, indicating that the entire molecules are necessary. Serotonin binding peptides do not bind the catecholamines. Morphine and apomorphine, however, do bind these catecholamines (with a binding constant for morphine of c. 4 X 10(4) per mole). The opiate antagonist naloxone and a number of other drugs do not bind catecholamines. Morphine, morphiceptin, and the enkephalins also retard the formation of colored reaction products by catecholamines in vitro. These results may help to explain observations that the enkephalins are co-stored and co-transmitted with dopamine and norepinephrine, and may provide a basis for the elucidation of other known cases of peptide-monoamine co-transmission. Possible implications for understanding opiate effects on catecholamines during addiction and withdrawal are discussed, and suggestions concerning drug design are made.