Dynorphin A inhibits nociceptin-converting enzyme from the rat spinal cord

Cysteine proteinase found in the spinal cord of rat, called nociceptin-conv erting enzyme (NCE), is competitively inhibited by dynorphin A and its frag ment des-[Tyr(1)]-DYN A. This proteinase converts orphanin FQ/nociceptin (O FQ/N) to two major fragments: OFQ/N(1-11) and further OFQ/N(1-6) with analg esic properties. Dynorphin A at the concentration of 10 muM increases K-M f rom 15.0 to 55.9 muM. The calculated K-i for this interaction was estimated at 3.7 muM. This observation may suggest an interaction between opioid and nociceptive systems which may be affected by the balance between opioid an d antiopioid systems. This balance between particular OFQ/N sequences that are derived from the same precursor and regulated by proteinases may play a n important role in pain. Interestingly, dynorphin B does not reveal a simi lar action on the NCE. (C) 2001 Academic Press.