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 alpha-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 cells 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 alpha-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.
Carr
D J
DJ
Department of Microbiology, LSU Medical Center, New Orleans 70112-1393.
Mayo
S
S
Gebhardt
B M
BM
Porter
J
J
D000818:Animals; D001921:Brain / Q000502:physiology*; D017292:Doxazosin / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000032:analysis; D013154:Spleen / Q000737:chemistry / Q000187:drug effects / Q000276:immunology
D007166:Immunosuppressive Agents; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D009020:Morphine; D017292:Doxazosin; D010646:Phentolamine