Abstract

The molecular forms of acetylcholinesterase in extracts of gastrocnemius muscle from four vertebrate species and in electric eel (Electrophorus) electric organ were separated and identified by low-salt precipitation and velocity sedimentation. The activity of the heavy insoluble (A12) form of human muscle acetylcholinesterase was inhibited by synthetic human beta-endorphin (500 mM). The homologous form in rat muscle extracts was poorly inhibited by human beta-endorphin at the same concentration, but was more effectively inhibited by camel beta-endorphin. The activities of heavy forms of pseudocholinesterase, present in small amounts in both species, were not reduced by beta-endorphin. Selective inhibition of homologous heavy forms of acetylcholinesterase activity by camel and human beta-endorphin was also seen in skeletal muscle extracts from frog and pigeon, but with decreased effectiveness. No inhibition was detectable in the heavy acetylcholinesterase form from extracts of electric organ tissue of the electric eel. The inhibition of heavy acetylcholinesterase activity in human muscle by human beta-endorphin was dependent on the presence of its NH2-terminal pentapeptide sequence. Maximal inhibitory potency depended on the presence of the entire amino acid sequence, since potency was considerably reduced in synthetic peptide analogues lacking either middle or COOH-terminal segments of beta-endorphin. The relative potency of beta-endorphin from various species as inhibitors of rat heavy acetylcholinesterase activity was also investigated. beta-Endorphin sequences most closely resembling that of the rat peptide (camel, equine) were most potent, whereas those with sequence differences of more than one amino-acid were less potent (turkey, human) or had no inhibitory activity (ostrich). The selective inhibition of heavy acetylcholinesterase by beta-endorphin thus exhibits species specificity, even among mammals, in which homologues of this molecular form of the enzyme are otherwise indistinguishable.