Effect and Mechanism of Opioid Receptor Antagonist on Allograft Rejection

Objective In our previous work, naltrexone, a common opioid receptor antagonist was found to be able to inhibit transplantation rejection. Here, we profound this work by using a specific opioid δ receptor antagonist naltrindole to explore the mechanism of the transplantation rejection related to opioid.Methods A transplantation model was used in the in vivo experiments, in which the cardiac tissue of newborn C57 mouse was transplanted into subcutis of the ear of Balb/c mouse. Mixed and cultured together, lymphocytes from two different strains of mice were used in the in vitro experiments. 3H TdR uptake (Bq) was measured to show the mixed lymphocyte reaction. The total RNA of the mixed lymphocytes cultured for certein time was hybridized with [ 32 P] PPE cDNA probe.Results (1)The survival of the transplanted tissues of naltrindole administrated group was significantly longer than that of naltrexone administrated group. (2) Treated with naltrexone or naltrindole, the proliferation of the mixed lymphocytes was inhibited in dose dependent style.And the inhibitory effect of naltrindole was greater than that of naltrexone. (3) It was also found that enkephalin increased the mixed lymphocyte reaction at the early stage of culturing in a concentration dependent biphasic manner, and nal trindole could totally antagonize its effect .(4) There was transcription of PPE mRNA in mixed lymphocytes cultured after certain time (10, 20, 40 and 60 h). Induced immune reaction and its endogenou ligand of this effect was most probably enkephalin.Conclusions (1) The results suggest that δ opioid receptor is involved in the antigen induced immune reaction and its endogenou ligand of this effect is probably enkephalin. (2) The activated immune cells in rejection is likely to produce enkephalin, which works as an stimulating factor for rejecting immune reaction.