Endo-oligopeptidase (EC 3.4.22.19), an enzyme capable of generating enkephalin by single cleavage from enkephalin-containing peptides, was examined in several areas of the central nervous system (CNS) as well as in the immune and endocrine tissues of rats chronically treated with morphine and submitted to naloxone-induced withdrawal. A specific fluorogenic substrate was used to determine the endopeptidase 22.19 activity. A non-uniform increase in endopeptidase 22.19 activity was detected in the CNS. The highest increase in endopeptidase 22.19 specific activity was found in the dorsal hippocampus (about 3.5-fold higher than control), followed by occipital and frontal cortex, substantia nigra, thalamus and hypothalamus. In peripheral tissues, a significant decrease of endopeptidase 22.19 was observed in the pineal gland, whereas the morphine withdrawal syndrome caused a slight but significant increase in lymphoid tissues such as lymph nodes and thymus. These findings are indicative of a possible participation of endopeptidase 22.19 in naloxone-induced withdrawal.
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