ROLE OF CENTRAL MU-OPIOID RECEPTORS IN THE MODULATION OF NITRIC-OXIDEPRODUCTION BY SPLENOCYTES

Previous studies have shown that administration of morphine results in alterations of splenic macrophage nitric oxide production. The presen t studies were conducted to determine the subtype of opioid receptor i nvolved in the modulation of macrophage nitric oxide production. Moreo ver, the present work was directed at determining whether nitric oxide production is regulated through opioid receptors in the central nervo us system (CNS) or via opioid receptors found directly on splenocytes. The study shows that intracerebroventricular (ICV) administration of the mu-selective opioid agonist, DAMGO, to rats dose-dependently incre ases the production of nitric oxide by splenocytes stimulated with tox ic shock syndrome toxin (TSST-1). The effect of DAMGO is blocked by pr ior ICV administration of N-methylnaltrexone, In contrast, ICV adminis tration of the kappa-selective agonist, U69,593, and the delta-selecti ve agonist, DPDPE, have no significant effect on the production of nit ric oxide. Furthermore, the in vitro administration of DAMGO, DPDPE, o r U69,593 to splenocytes cultures does not significantly alter the pro duction of nitric oxide by splenocytes. In addition, the present work shows that elevation of nitric oxide production by ICV administration of DAMGO produces functional changes in splenic lymphocytes. Collectiv ely, these results indicate that mu-opioid receptors within the CNS ar e involved in the regulation of splenic nitric oxide production. (C) 1 998 Elsevier Science B.V. All rights reserved.