Inhibition of calcium mobilization is an early event in opiate-induced immunosuppression.
Morphine administered as a subcutaneous implant inhibits the initial increase in cytoplasmic free-calcium [Ca2+]i induced by mitogens in mouse splenocytes. This effect was not reproduced by incubation of splenocytes with morphine (10(-8)-10(-4) M). Analysis of splenocyte subpopulations demonstrates that this effect was manifest in both B and T cells. However, within T cell subpopulations, CD4+ but not CD8+ cells were affected. Adrenalectomy abolished this effect of morphine in CD4+ T but not CD4-, CD8- spleen cells (most likely Thy 1.2- B cells). Moreover, simultaneous administration of the opiate antagonist naltrexone blocked the effect of morphine in CD4-, CD8- spleen cells, but not in CD4+ T cells. These data indicate that the effects of morphine on mitogen-stimulated increase in [Ca2+]i may be mediated through distinct glucocorticoid-dependent and -independent mechanisms. The morphine-induced inhibition of an increase in [Ca2+]i in immune cells reported here may be an early event mediating opiate-induced immunosuppression.
Sei
Y
Y
Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
McIntyre
T
T
Fride
E
E
Yoshimoto
K
K
Skolnick
P
P
Arora
P K
PK
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000493:pharmacokinetics*; D003208:Concanavalin A / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D009294:Narcotics; D003208:Concanavalin A; D009271:Naltrexone; D009020:Morphine; D003907:Dexamethasone; D002118:Calcium