PT  - JOURNAL ARTICLE
AU  - Fecho, K
AU  - Maslonek, K A
AU  - Dykstra, L A
AU  - Lysle, D T
TI  - Mechanisms whereby macrophage-derived nitric oxide is involved in morphine-induced suppression of splenic lymphocyte proliferation.
DP  - 1995 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 477--483
VI  - 272
IP  - 2
4099  - http://jpet.aspetjournals.org/content/272/2/477.short
4100  - http://jpet.aspetjournals.org/content/272/2/477.full
SO  - J Pharmacol Exp Ther1995 Feb 01; 272
AB  - Previous research by our laboratory demonstrated that in vivo administration of morphine to rats suppresses concanavalin-A (Con-A)-stimulated proliferation of splenic lymphocytes in a dose-dependent, naltrexone-reversible manner. More recently, we showed that morphine-induced suppression of Con A-stimulated proliferation of lymphocytes depends on an increase in macrophage production of nitric oxide (NO) in splenocyte cultures. The present study investigated effector mechanisms through which morphine-induced increases in macrophage-derived NO decrease lymphocyte proliferation in Con A-stimulated splenocyte cultures. The results show that the addition of hemoglobin, a scavenger of extracellular NO, to Con A-stimulated splenocyte cultures dose-dependently attenuates the suppressive effect of morphine on proliferation. The addition of superoxide dismutase, a scavenger of superoxide anions, to splenocyte cultures does not antagonize the suppressive effect of morphine on Con A-stimulated proliferation. The addition of either methylene blue or 6-anilino-5, 8-quinolinedione (LY 83583), two inhibitors of soluble guanylate cyclase, to splenocyte cultures dose-dependently antagonizes the suppressive effect of morphine on Con A-stimulated proliferation. Taken together with our previous results, the present results suggest that in vivo administration of morphine increases the synthesis and extracellular release of NO from macrophages in Con A-stimulated splenocyte cultures. The results further suggest that the formation of the oxidant peroxynitrite through a reaction between NO and superoxide anion does not contribute significantly to the suppression of lymphocyte proliferation; instead, the activation of soluble guanylate cyclase by NO in target cells, most likely the lymphocytes, accounts more completely for the morphine-induced suppression of lymphocyte proliferation.