INDIRECT INVOLVEMENT OF THE OPIOID SYSTEM IN REGULATION OF PAIN SENSITIVITY BY PEPTIDE-FRAGMENTS MP(1) AND MP(2)

The synthetic myelopeptide analogs MP(1) and MP(2) at doses 10(-13) an d 10(-8) g/animal naloxone-dependently modulate the pain sensitivity o f mice. The binding of the peptides to opioid receptors of mouse brain membranes was studied by radioligand assay. MP(1) non-specifically di splaces [H-3]DAGO (IC50 = 7.3 . 10(-5) M) and [H-3]DSLET (IC50=7.0 . 1 0(-5) M). The hexapeptide MP(2) does not significantly displaces these selective ligands. These data indicate that the hypoalgesic effect of the peptides is not due to direct interaction with opioid receptors. However, the naloxone-dependence of the effect suggests an indirect in volvement of the opioidergic system.