CENTRAL ALPHA-ADRENERGIC INVOLVEMENT IN MORPHINE-MEDIATED SUPPRESSION OF SPLENIC NATURAL-KILLER ACTIVITY

Alpha(1)-adrenergic pathways are involved in morphine-induced suppression of murine splenic NK activity. To investigate the level of involvement following morphine administration, the peripheral acting cu-adrenoceptor antagonist doxazosin and the broad acting alpha-adrenoceptor antagonist phentolamine were employed. Mice preadministered phentolamine (2.0 mg/kg) exhibited a modest but insignificant suppression of splenic NK activity following morphine administration while mice preadministered doxazosin (1.0 mg/kg) or vehicle showed a significant decrease in splenic NK activity following morphine administration. Morphine was also found to significantly (P < 0.01) increase splenic serotonin levels (14.88 +/- 1.62 ng/mg) relative to saline-treated controls (7.3 +/- 0.9 ng/mg). Both phentolamine and doxazosin pretreatment completely or partially blocked morphine-mediated elevation of splenic serotonin levels, respectively, Morphine administration decreased the ability of NK eels to form conjugates with target (YAC-1 lymphoma) cells and decreased the number of active killer cells within the conjugate population. Collectively, these results implicate central cu-adrenergic involvement following acute morphine administration in suppressing splenic NK activity indirectly through a reduction in the number of effector-target conjugates and active cytolytic effector cells.