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 immune function. The present study demonstrated that both the sigma receptor ligand igmesine: (+)-N-cyclopropylmethy-N-methyl-1, 4-diphenyl-1-yl-but-3-en-1-ylamine, hydrochloride (JO 1784) (10(-7) and 10(-5) M) and neuropeptide Y (10(-9) and 10(-7) M) in vitro significantly reduced neutrophil phagocytosis and decreased mitogen stimulated lymphocyte proliferation. By contrast, central administration of JO 1784 (0.5 and 5 microg/5 microl) significantly reduced the activity of neutrophil phagocytosis, but enhanced lymphocyte proliferation without changing the serum concentration of corticosterone. Neuropeptide Y (10(-9) and 10(-7) M), following intracerebroventricular infusion, also decreased the neutrophil response, but significantly raised the corticosterone concentration. These results indicate that different mechanisms (involving various neurotransmitters and their receptors, changes in the activity of the hypothalamic-pituitary-adrenal axis, or sigma receptor subtypes) may be involved in the central effects of JO 1784 and neuropeptide Y.
Song
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Department of Pharmacology, University College Galway, Ireland.
Leonard
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BE
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003521:Cyclopropanes / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007202:Indicators and Reagents; D007276:Injections, Intraventricular; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*
D002934:Cinnamates; D003521:Cyclopropanes; D007202:Indicators and Reagents; D008934:Mitogens; D009478:Neuropeptide Y; D017480:Receptors, sigma; D003345:Corticosterone; C065310:igmesine