Macrophage-derived nitric oxide is involved in the depressed concanavalin A responsiveness of splenic lymphocytes from rats administered morphine in vivo.
The present study examined the role of macrophage-derived nitric oxide in the suppressive effect of in vivo morphine administration on Con A-stimulated proliferation of splenic lymphocytes in rats. The results showed that concentrations of nitrite are significantly greater in Con A-stimulated splenocyte cultures from morphine-treated rats than in cultures from saline-treated rats, and that the depletion of macrophages from splenocyte cultures abolishes the suppressive effect of morphine on Con A-stimulated proliferation. Moreover, the addition of NG-monomethyl-L-arginine (NMMA) to Con A-stimulated splenocyte cultures attenuates the suppressive effect of morphine on mitogenic responsiveness. The addition of excess L-arginine to splenocyte cultures containing NMMA reverses the effect of NMMA and restores morphine's suppressive effect on Con A-stimulated proliferation, but the addition of D-arginine to splenocyte cultures containing NMMA does not restore the suppressive effect of morphine. Taken together, these findings demonstrate that the suppressive effect of in vivo morphine administration on Con A-stimulated proliferation of splenic lymphocytes involves macrophage-derived nitric oxide.
Fecho
K
K
Department of Psychology, University of North Carolina at Chapel Hill 27599.
Maslonek
K A
KA
Coussons-Read
M E
ME
Dykstra
L A
LA
Lysle
D T
DT
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019323:omega-N-Methylarginine
D011943:Receptors, Adrenergic, beta; D003208:Concanavalin A; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine