The metabolism of the opioid peptide [3H]dynorphin 1-8 by slices of central nervous system (c.n.s.) and peripheral tissues, from the rat and guinea-pig has been studied. Rat spinal cord rapidly degraded [3H]dynorphin 1-8, the N-terminal tyrosine residue being most susceptible to hydrolysis and therefore forming the major metabolite. Pre-treatment of the metabolizing tissue with a standard cocktail of enzyme inhibitors decreased the degradation of [3H]dynorphin 1-8 at both the N- and C-termini. However, inclusion of this enzyme inhibitor cocktail revealed the activity of a further enzyme, an endopeptidase, capable of cleaving the leucine5–arginine6 bond within the octapeptide liberating the opioid pentapeptide [Leu]enkephalin. This pattern of metabolism was observed across all rat brain regions and periphery.

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