Effects of Livagen and Epitalon, New Peptide Bioregulators, on Enkephalin-Degrading Enzymes from Human Serum

The effects of new peptide bioregulators—Livagen (Lys-Glu-Asp-Ala) and Epitalon (Ala-Glu-Asp-Gly)—on the endogenous opioid system was studied. In particular, attention was focused on their ability to change the activity of enkephalin-degrading enzymes of blood serum and interact with opioid receptors of the brain membrane fraction. Enkephalinase activity was assayed in vitro by the rate of ³H-Leu-enkephalin hydrolysis in the presence of Livagen and Epitalon. These peptides inhibited enkephalin-degrading enzymes of human serum. Livagen proved to be more efficient than some well-known peptidase inhibitors, such as puromycin, leupeptin, and D-PAM. The dose–inhibitory effect curves for Livagen and Epitalon were plotted; their IC₅₀ equaled 20 and 500 M, respectively. The interaction between the peptides and opioid receptors was estimated using a radioreceptor method with [³H][D-Ala², D-Leu⁵]-enkephalin. No interaction was observed between the peptides and - or -opioid receptors of the membrane fraction from the rat brain.