EFFECT OF OPIOID RECEPTOR ANTAGONIST NALTRINDOLE ON TRANSPLANTATION REJECTION

AIM: To investigate the subtype of the opioid receptors involved in transplantation rejection. METHODS: The in vivo experiment: Cardiac tissue of the newborn KM mouse was transplanted into the ear of Balb/c mouse. The survival of the transplanted tissue was shown with its electrocardiogram. Naltrexone or naltrindole (selective δ opioid receptor antagonist) was injected ip twice per day for 10 days (5 mg.kg^-1 body weight). The in vitro experiment: Lymphocytes from two different strains of mice were mixed and cultured together. Naltrexone, naltrindole or enkephalin (a selective δ opioid receptor agonist) was added into the culture fluid. 3H-TdR uptake (cpm) was measured to show the mixed lymphocyte reaction. RESULTS: The mean survival time of the transplanted tissues of naltrindole-treated group was 15.6±2.4 days, which was significantly longer (t-test, P<0.05, n=6) than that of naltrexone-treated group (10.9±1.1 days). While the latter was longer (t-test, P<0.05, n=6) than that of normal saline injection group (8.0±0.5　days) and control group (8.1±0.9 days). The mixed lymphocyte reactions, after treated with naltrexone at concentration 10^-8, 10^-6 and 10^-4 　mol.L^-1, were 3196±810, 1268±320 and 432±110 min-1, respectively. The result showed an inhibitory effect of naltrexone on mixed lymphocyte reaction in dose response way. While the mixed lymphocyte reaction treated with naltrindole at concentrations 10^-10, 10^-8, 10^-6 and 10^-4 mol.L^-1 were 2021±101, 1611±450, 630±160 and 455±105 min^-1, which was significantly decreased(ANOVA, P<0.05) as compared with the naltrexone group. It was also found that enkephalin increased the mixed lymphocyte reaction at the early stage of culture. CONCLUSION: The results suggest that δ opioid receptor is involved in the antigen-induced immune reaction and the δ receptor antagonist naltrindole can inhibit the transplantation rejection.