COMPARISON BETWEEN THE EFFECTS OF SIGMA-RECEPTOR LIGAND JO-1784 AND NEUROPEPTIDE-Y ON IMMUNE FUNCTIONS

Recent evidence suggests that sigma receptor ligands and neuropeptide Y may act through the same pathways to modulate centrally mediated imm une function. The present study demonstrated that both the a receptor ligand igmesine: (+)-N-cyclopropylmethy-N-methyl-1, 4-diphenyl-1-yl-bu t-3-en-1-ylamine, hydrochloride (JO 1784) (10(-7) and 10(-5) M) and ne uropeptide Y(10(-9) and 10(-7) M) in vitro significantly reduced neutr ophil phagocytosis and decreased mitogen stimulated lymphocyte prolife ration. By contrast, central administration of JO 1784 (0.5 and 5 mu g /5 mu l) significantly reduced the activity of neutrophil phagocytosis , but enhanced lymphocyte proliferation without changing the serum con centration of corticosterone. Neuropeptide Y (10(-9) and 10(-7) M), fo llowing intracerebroventricular infusion, also decreased the neutrophi l response, but significantly raised the corticosterone concentration. These results indicate that different mechanisms (involving various n eurotransmitters and their receptors, changes in the activity of the h ypothalamic-pituitary-adrenal axis, or a receptor subtypes) may be inv olved in the central effects of JO 1784 and neuropeptide Y. (C) 1998 E lsevier Science B.V.