SYNTHESIS, PAIN MODULATION AND IMMUNOACTIVITY OF NOCICEPTIN AND ITS FRAGMENTS

AIM：To analyse the structure-activity relationship of nociceptin (NC) by the changes of pain modulation and the sequence of its four fragments(NC(1-15)NH₂, NC(1-13)NH₂, NC(1-11)NH₂, and NC(1-5)NH₂), and to evaluate the immuno-activity of NC and its fragments. METHODS: Peptides were synthesized by solid phase peptide synthesis. The hyperalgesia and antagnism to analgesia induced by morphin were evaluated with tail flick method. Percentage of rosette forming cell and the red cell immuno activity were used to determine the effect on immuno system. RESULTS: NC and its fragments showed hyporelgesia activity and antagnized morphine induced analgesia, but the activities of NC(1-11)NH₂ and NC(1-5)NH₂ were 100 times lower than the activity of NC. NC(1-13)NH₂ and NC(1-15)NH₂ shared the same activity with NC. The percentage of rosette formed by activated T cell could be enhanced by NC and its fragments. NC(1-11)NH₂ was shown to enhance the red cell immuno activity only at the dose of 0.3 nmol.kg^-1. NC(1-5)NH₂ showed no effect on RCIA. CONCLUSION: The entire sequence of NC may be not required for full hyperalgesic activity because NC(1-13)NH₂ shares the same activity with NC. NC(1-11)NH₂ and NC(1-5)NH₂ have very low activity so the C terminal plays important role in the structure-activity relationship of NC.