Tyr-W-MIF-1 attenuates down-regulation of opiate receptors in SH-SY5Y human neuroblastoma cells

Down-regulation of opiate receptors is demonstrated more easily in vitro than in vivo. The possible role of endogenous opiate-modulating Peptides in preventing such down-regulation was investigated by addition of Tyr-W-MIF-1 to an in vitro preparation, the human neuroblastoma cell line SH-SY5Y, in which down-regulation of opiate receptors has been demonstrated previously. Although both morphine and Met-enkephalin down-regulated mu and delta receptors after chronic (24 h) exposure in serum-free medium, Tyr-W-MIF-1, at doses of up to 100 microM, did not affect receptor number when administered alone. This lack of effect could not be attributed to degradation of the peptide during chronic treatment because high-performance liquid chromatography showed that 79% of the peptide remained intact after a 24-h incubation. When coadministered with 3 microM morphine, Tyr-W-MIF-1 dose-dependently attenuated morphine-induced down-regulation of both mu and delta receptors. Down-regulation of mu receptors by the selective agonist PL017 was also attenuated by Tyr-W-MIF-1, but down-regulation of delta receptors by the selective agonist DPDPE was not. These studies indicate that endogenous opiate modulators may play a role in opiate tolerance at the level of receptor down-regulation.