Opioid agonist modulation of cytoplasmic free Ca2+ level in concanavalin A-stimulated mouse lymphocytes

In this study the influence of mu-, delta-, and kappa-selective opioid agon ists (DAMGO; DSLET, and dynorphin A (1-13)) on cytoplasmic free Ca2+ ([Ca2](i)) level in normal and colicanavalin-A (Con A)-activated mouse lymphocyt es was investigated. [Ca2+](i) was measured using the fluorescent dye FURA- 2AM. The opioid peptides at 10(-12)-10(-7) M induced some increase in [Ca2](i) in non-activated lymphocytes; However, DAMGO and DSLET (10(-13)-10(-7) M) considerably inhibited a Con A-induced increase in [Ca2+](i). The inhib iting effect of both peptides was higher after 20-min preincubation compare to 2-h preincubation. The effect of the kappa-agonist dynorphin A (1-13) w as significantly different depending on the duration. of cell pretreatment and the concentration of the peptide used. After preincubation for 20 min a t low concentrations (10(-12)-10(-11) M) it slightly stimulated, while at h igher (10(-10)-10(-7) M) concentrations it inhibited lymphocyte response to Con A. After preincubation for 2 h, pronounced stimulation of mitogen-indu ced Ca2+ flux was observed at peptide concentration 10(-9) M. The effects o f opioids were antagonized by naloxone. These data indicate that functional ly active opioid receptors expressed on lymphocytes could be involved, in e arly stages of mitogen activation.