[Effects of opioids on Ca2+ flux of polymorphonuclear leukocytes]

The effects of opioids on Ca2+ influx were evaluated using rat polymorphonuclear leukocytes, comparing with those of nicardipine and TMB-8, 8-(N, N diethyl amino) 3, 4, 5 trimethoxybenzoate. Selective opioid kappa-agonist, U-50488H, inhibited Ca2+ influx caused by f-Met-Leu-Phe (fMLP). U-50488H also strongly inhibited the elevation of intracellular free Ca2+ concentration in Ca2+ free medium. In contrast, mu-agonist, morphine showed no effects. The purified enantiomers of U-50488H exerted no difference in their effects on Ca2+ mobilization of PMNs, and naloxone did not antagonize the effects of U-50488H. Both nicardipine and TMB-8 inhibited the Ca2+ flux. The inhibitory effects of TMB-8 were potentiated by lowering extracellular free Ca2+. These results suggest that U-50488H may interfere with the Ca2+ regulatory system of PMNs via opioid receptor non-mediated pathway. The effect was suspected to be caused by selective inhibition of Ca2+ release from intracellular Ca2+ store sites by affecting post-receptor mechanisms of f-MLP.